---
_id: '12288'
abstract:
- lang: eng
  text: To understand the function of neuronal circuits, it is crucial to disentangle
    the connectivity patterns within the network. However, most tools currently used
    to explore connectivity have low throughput, low selectivity, or limited accessibility.
    Here, we report the development of an improved packaging system for the production
    of the highly neurotropic RVdGenvA-CVS-N2c rabies viral vectors, yielding titers
    orders of magnitude higher with no background contamination, at a fraction of
    the production time, while preserving the efficiency of transsynaptic labeling.
    Along with the production pipeline, we developed suites of ‘starter’ AAV and bicistronic
    RVdG-CVS-N2c vectors, enabling retrograde labeling from a wide range of neuronal
    populations, tailored for diverse experimental requirements. We demonstrate the
    power and flexibility of the new system by uncovering hidden local and distal
    inhibitory connections in the mouse hippocampal formation and by imaging the functional
    properties of a cortical microcircuit across weeks. Our novel production pipeline
    provides a convenient approach to generate new rabies vectors, while our toolkit
    flexibly and efficiently expands the current capacity to label, manipulate and
    image the neuronal activity of interconnected neuronal circuits in vitro and in
    vivo.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: We thank F Marr for technical assistance, A Murray for RVdG-CVS-N2c
  viruses and Neuro2A packaging cell-lines and J Watson for reading the manuscript.
  This research was supported by the Scientific Service Units (SSU) of IST-Austria
  through resources provided by the Imaging and Optics Facility (IOF) and the Preclinical
  Facility (PCF). This project was funded by the European Research Council (ERC) under
  the European Union’s Horizon 2020 research and innovation programme (ERC advanced
  grant No 692692, PJ, ERC starting grant No 756502, MJ), the Fond zur Förderung der
  Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award, PJ), the Human Frontier
  Science Program (LT000256/2018-L, AS) and EMBO (ALTF 1098-2017, AS).
article_number: '79848'
article_processing_charge: No
article_type: original
author:
- first_name: Anton L
  full_name: Sumser, Anton L
  id: 3320A096-F248-11E8-B48F-1D18A9856A87
  last_name: Sumser
  orcid: 0000-0002-4792-1881
- first_name: Maximilian A
  full_name: Jösch, Maximilian A
  id: 2BD278E6-F248-11E8-B48F-1D18A9856A87
  last_name: Jösch
  orcid: 0000-0002-3937-1330
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
- first_name: Yoav
  full_name: Ben Simon, Yoav
  id: 43DF3136-F248-11E8-B48F-1D18A9856A87
  last_name: Ben Simon
citation:
  ama: Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. Fast, high-throughput production
    of improved rabies viral vectors for specific, efficient and versatile transsynaptic
    retrograde labeling. <i>eLife</i>. 2022;11. doi:<a href="https://doi.org/10.7554/elife.79848">10.7554/elife.79848</a>
  apa: Sumser, A. L., Jösch, M. A., Jonas, P. M., &#38; Ben Simon, Y. (2022). Fast,
    high-throughput production of improved rabies viral vectors for specific, efficient
    and versatile transsynaptic retrograde labeling. <i>ELife</i>. eLife Sciences
    Publications. <a href="https://doi.org/10.7554/elife.79848">https://doi.org/10.7554/elife.79848</a>
  chicago: Sumser, Anton L, Maximilian A Jösch, Peter M Jonas, and Yoav Ben Simon.
    “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific,
    Efficient and Versatile Transsynaptic Retrograde Labeling.” <i>ELife</i>. eLife
    Sciences Publications, 2022. <a href="https://doi.org/10.7554/elife.79848">https://doi.org/10.7554/elife.79848</a>.
  ieee: A. L. Sumser, M. A. Jösch, P. M. Jonas, and Y. Ben Simon, “Fast, high-throughput
    production of improved rabies viral vectors for specific, efficient and versatile
    transsynaptic retrograde labeling,” <i>eLife</i>, vol. 11. eLife Sciences Publications,
    2022.
  ista: Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. 2022. Fast, high-throughput production
    of improved rabies viral vectors for specific, efficient and versatile transsynaptic
    retrograde labeling. eLife. 11, 79848.
  mla: Sumser, Anton L., et al. “Fast, High-Throughput Production of Improved Rabies
    Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.”
    <i>ELife</i>, vol. 11, 79848, eLife Sciences Publications, 2022, doi:<a href="https://doi.org/10.7554/elife.79848">10.7554/elife.79848</a>.
  short: A.L. Sumser, M.A. Jösch, P.M. Jonas, Y. Ben Simon, ELife 11 (2022).
corr_author: '1'
date_created: 2023-01-16T10:04:15Z
date_published: 2022-09-15T00:00:00Z
date_updated: 2025-04-15T08:29:05Z
day: '15'
ddc:
- '570'
department:
- _id: MaJö
- _id: PeJo
doi: 10.7554/elife.79848
ec_funded: 1
external_id:
  isi:
  - '000892204300001'
  pmid:
  - '36040301'
file:
- access_level: open_access
  checksum: 5a2a65e3e7225090c3d8199f3bbd7b7b
  content_type: application/pdf
  creator: dernst
  date_created: 2023-01-30T11:50:53Z
  date_updated: 2023-01-30T11:50:53Z
  file_id: '12463'
  file_name: 2022_eLife_Sumser.pdf
  file_size: 8506811
  relation: main_file
  success: 1
file_date_updated: 2023-01-30T11:50:53Z
has_accepted_license: '1'
intvolume: '        11'
isi: 1
keyword:
- General Immunology and Microbiology
- General Biochemistry
- Genetics and Molecular Biology
- General Medicine
- General Neuroscience
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 2634E9D2-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '756502'
  name: Circuits of Visual Attention
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z00312
  name: Synaptic communication in neuronal microcircuits
- _id: 266D407A-B435-11E9-9278-68D0E5697425
  grant_number: LT000256
  name: Neuronal networks of salience and spatial detection in the murine superior
    colliculus
- _id: 264FEA02-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 1098-2017
  name: Connecting sensory with motor processing in the superior colliculus
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Fast, high-throughput production of improved rabies viral vectors for specific,
  efficient and versatile transsynaptic retrograde labeling
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 11
year: '2022'
...
---
_id: '10763'
abstract:
- lang: eng
  text: "AMPA-type glutamate receptors (AMPARs) mediate rapid signal transmission
    at excitatory\r\nsynapses in the brain. Glutamate binding to the receptor’s ligand-binding
    domains (LBDs)\r\nleads to ion channel activation and desensitization. Gating
    kinetics shape synaptic transmission\r\nand are strongly modulated by transmembrane
    AMPAR regulatory proteins (TARPs)\r\nthrough currently incompletely resolved mechanisms.
    Here, electron cryo-microscopy\r\nstructures of the GluA1/2 TARP-γ8 complex, in
    both open and desensitized states\r\n(at 3.5 Å), reveal state-selective engagement
    of the LBDs by the large TARP-γ8 loop (‘β1’),\r\nelucidating how this TARP stabilizes
    specific gating states. We further show how TARPs alter\r\nchannel rectification,
    by interacting with the pore helix of the selectivity filter. Lastly, we\r\nreveal
    that the Q/R-editing site couples the channel constriction at the filter entrance
    to the\r\ngate, and forms the major cation binding site in the conduction path.
    Our results provide a\r\nmechanistic framework of how TARPs modulate AMPAR gating
    and conductance."
acknowledgement: "We thank Ondrej Cais for critical reading of the manuscript. We
  are grateful to LMB\r\nscientific computing and the EM facility for support, Paul
  Emsley for help with model\r\nbuilding and Takanori Nakane for helpful comments
  with Relion 3.1. This work was\r\nsupported by grants from the Medical Research
  Council (MC_U105174197) and BBSRC\r\n(BB/N002113/1) to I.H.G, and grants from the
  MCIN/AEI/ 10.13039/501100011033 and\r\n“ESF Investing in your future” to B.H (PID2019-106284GA-I00
  and RYC2018-025720-I)."
article_number: '734'
article_processing_charge: No
article_type: original
author:
- first_name: Beatriz
  full_name: Herguedas, Beatriz
  last_name: Herguedas
- first_name: Bianka K.
  full_name: Kohegyi, Bianka K.
  last_name: Kohegyi
- first_name: Jan Niklas
  full_name: Dohrke, Jan Niklas
  last_name: Dohrke
- first_name: Jake
  full_name: Watson, Jake
  id: 63836096-4690-11EA-BD4E-32803DDC885E
  last_name: Watson
  orcid: 0000-0002-8698-3823
- first_name: Danyang
  full_name: Zhang, Danyang
  last_name: Zhang
- first_name: Hinze
  full_name: Ho, Hinze
  last_name: Ho
- first_name: Saher A.
  full_name: Shaikh, Saher A.
  last_name: Shaikh
- first_name: Remigijus
  full_name: Lape, Remigijus
  last_name: Lape
- first_name: James M.
  full_name: Krieger, James M.
  last_name: Krieger
- first_name: Ingo H.
  full_name: Greger, Ingo H.
  last_name: Greger
citation:
  ama: Herguedas B, Kohegyi BK, Dohrke JN, et al. Mechanisms underlying TARP modulation
    of the GluA1/2-γ8 AMPA receptor. <i>Nature Communications</i>. 2022;13. doi:<a
    href="https://doi.org/10.1038/s41467-022-28404-7">10.1038/s41467-022-28404-7</a>
  apa: Herguedas, B., Kohegyi, B. K., Dohrke, J. N., Watson, J., Zhang, D., Ho, H.,
    … Greger, I. H. (2022). Mechanisms underlying TARP modulation of the GluA1/2-γ8
    AMPA receptor. <i>Nature Communications</i>. Springer Nature. <a href="https://doi.org/10.1038/s41467-022-28404-7">https://doi.org/10.1038/s41467-022-28404-7</a>
  chicago: Herguedas, Beatriz, Bianka K. Kohegyi, Jan Niklas Dohrke, Jake Watson,
    Danyang Zhang, Hinze Ho, Saher A. Shaikh, Remigijus Lape, James M. Krieger, and
    Ingo H. Greger. “Mechanisms Underlying TARP Modulation of the GluA1/2-Γ8 AMPA
    Receptor.” <i>Nature Communications</i>. Springer Nature, 2022. <a href="https://doi.org/10.1038/s41467-022-28404-7">https://doi.org/10.1038/s41467-022-28404-7</a>.
  ieee: B. Herguedas <i>et al.</i>, “Mechanisms underlying TARP modulation of the
    GluA1/2-γ8 AMPA receptor,” <i>Nature Communications</i>, vol. 13. Springer Nature,
    2022.
  ista: Herguedas B, Kohegyi BK, Dohrke JN, Watson J, Zhang D, Ho H, Shaikh SA, Lape
    R, Krieger JM, Greger IH. 2022. Mechanisms underlying TARP modulation of the GluA1/2-γ8
    AMPA receptor. Nature Communications. 13, 734.
  mla: Herguedas, Beatriz, et al. “Mechanisms Underlying TARP Modulation of the GluA1/2-Γ8
    AMPA Receptor.” <i>Nature Communications</i>, vol. 13, 734, Springer Nature, 2022,
    doi:<a href="https://doi.org/10.1038/s41467-022-28404-7">10.1038/s41467-022-28404-7</a>.
  short: B. Herguedas, B.K. Kohegyi, J.N. Dohrke, J. Watson, D. Zhang, H. Ho, S.A.
    Shaikh, R. Lape, J.M. Krieger, I.H. Greger, Nature Communications 13 (2022).
date_created: 2022-02-20T23:01:30Z
date_published: 2022-02-08T00:00:00Z
date_updated: 2026-04-02T12:14:43Z
day: '08'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1038/s41467-022-28404-7
external_id:
  isi:
  - '000757297200008'
  pmid:
  - '35136046'
file:
- access_level: open_access
  checksum: d86ee8eabe8b794730729ffbb1a8832e
  content_type: application/pdf
  creator: dernst
  date_created: 2022-02-21T07:59:32Z
  date_updated: 2022-02-21T07:59:32Z
  file_id: '10778'
  file_name: 2022_NatureCommunications_Herguedas.pdf
  file_size: 2625540
  relation: main_file
  success: 1
file_date_updated: 2022-02-21T07:59:32Z
has_accepted_license: '1'
intvolume: '        13'
isi: 1
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
publication: Nature Communications
publication_identifier:
  eissn:
  - 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 13
year: '2022'
...
---
OA_place: publisher
_id: '11196'
abstract:
- lang: eng
  text: "One of the fundamental questions in Neuroscience is how the structure of
    synapses and their physiological properties are related. While synaptic transmission
    remains a dynamic process, electron microscopy provides images with comparably
    low temporal resolution (Studer et al., 2014). The current work overcomes this
    challenge and describes an improved “Flash and Freeze” technique (Watanabe et
    al., 2013a; Watanabe et al., 2013b) to study synaptic transmission at the hippocampal
    mossy fiber-CA3 pyramidal neuron synapses, using mouse acute brain slices and
    organotypic slices culture. The improved method allowed for selective stimulation
    of presynaptic mossy fiber boutons and the observation of synaptic vesicle pool
    dynamics at the active zones. Our results uncovered several intriguing morphological
    features of mossy fiber boutons. First, the docked vesicle pool was largely depleted
    (more than 70%) after stimulation, implying that the docked synaptic vesicles
    pool and readily releasable pool are vastly overlapping in mossy fiber boutons.
    Second, the synaptic vesicles are skewed towards larger diameters, displaying
    a wide range of sizes. An increase in the mean diameter of synaptic vesicles,
    after single and repetitive stimulation, suggests that smaller vesicles have a
    higher release probability. Third, we observed putative endocytotic structures
    after moderate light stimulation, matching the timing of previously described
    ultrafast endocytosis (Watanabe et al., 2013a; Delvendahl et al., 2016). \r\n\tIn
    addition, synaptic transmission depends on a sophisticated system of protein machinery
    and calcium channels (Südhof, 2013b), which amplifies the challenge in studying
    synaptic communication as these interactions can be potentially modified during
    synaptic plasticity. And although recent study elucidated the potential correlation
    between physiological and morphological properties of synapses during synaptic
    plasticity (Vandael et al., 2020), the molecular underpinning of it remains unknown.
    Thus, the presented work tries to overcome this challenge and aims to pinpoint
    changes in the molecular architecture at hippocampal mossy fiber bouton synapses
    during short- and long-term potentiation (STP and LTP), we combined chemical potentiation,
    with the application of a cyclic adenosine monophosphate agonist (i.e. forskolin)
    and freeze-fracture replica immunolabelling. This method allowed the localization
    of membrane-bound proteins with nanometer precision within the active zone, in
    particular, P/Q-type calcium channels and synaptic vesicle priming proteins Munc13-1/2.
    First, we found that the number of clusters of Munc13-1 in the mossy fiber bouton
    active zone increased significantly during STP, but decreased to lower than the
    control value during LTP. Secondly, although the distance between the calcium
    channels and Munc13-1s did not change after induction of STP, it shortened during
    the LTP phase. Additionally, forskolin did not affect Munc13-2 distribution during
    STP and LTP. These results indicate the existence of two distinct mechanisms that
    govern STP and LTP at mossy fiber bouton synapses: an increase in the readily
    realizable pool in the case of STP and a potential increase in release probability
    during LTP. “Flash and freeze” and functional electron microscopy, are versatile
    methods that can be successfully applied to intact brain circuits to study synaptic
    transmission even at the molecular level.\r\n"
acknowledged_ssus:
- _id: EM-Fac
- _id: PreCl
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Olena
  full_name: Kim, Olena
  id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87
  last_name: Kim
  orcid: 0000-0003-2344-1039
citation:
  ama: Kim O. Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses.
    2022. doi:<a href="https://doi.org/10.15479/at:ista:11196">10.15479/at:ista:11196</a>
  apa: Kim, O. (2022). <i>Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal
    neuron synapses</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:11196">https://doi.org/10.15479/at:ista:11196</a>
  chicago: Kim, Olena. “Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal
    Neuron Synapses.” Institute of Science and Technology Austria, 2022. <a href="https://doi.org/10.15479/at:ista:11196">https://doi.org/10.15479/at:ista:11196</a>.
  ieee: O. Kim, “Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron
    synapses,” Institute of Science and Technology Austria, 2022.
  ista: Kim O. 2022. Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron
    synapses. Institute of Science and Technology Austria.
  mla: Kim, Olena. <i>Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron
    Synapses</i>. Institute of Science and Technology Austria, 2022, doi:<a href="https://doi.org/10.15479/at:ista:11196">10.15479/at:ista:11196</a>.
  short: O. Kim, Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron
    Synapses, Institute of Science and Technology Austria, 2022.
corr_author: '1'
date_created: 2022-04-20T09:47:12Z
date_published: 2022-04-20T00:00:00Z
date_updated: 2026-04-07T14:22:20Z
day: '20'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: PeJo
- _id: GradSch
doi: 10.15479/at:ista:11196
ec_funded: 1
file:
- access_level: open_access
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  date_created: 2022-04-20T14:21:56Z
  date_updated: 2023-04-20T22:30:03Z
  embargo: 2023-04-19
  file_id: '11220'
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  creator: okim
  date_created: 2022-04-20T14:22:56Z
  date_updated: 2023-04-20T22:30:03Z
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  file_id: '11221'
  file_name: KIM_thesis_final.zip
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file_date_updated: 2023-04-20T22:30:03Z
has_accepted_license: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '04'
oa: 1
oa_version: Published Version
page: '132'
project:
- _id: 25BAF7B2-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '708497'
  name: Presynaptic calcium channels distribution and impact on coupling at the hippocampal
    mossy fiber synapse
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 25C3DBB6-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W01205
  name: Zellkommunikation in Gesundheit und Krankheit
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z00312
  name: Synaptic communication in neuronal microcircuits
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '7473'
    relation: part_of_dissertation
    status: public
  - id: '11222'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
title: Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2022'
...
---
OA_place: repository
_id: '11943'
abstract:
- lang: eng
  text: Complex wiring between neurons underlies the information-processing network
    enabling all brain functions, including cognition and memory. For understanding
    how the network is structured, processes information, and changes over time, comprehensive
    visualization of the architecture of living brain tissue with its cellular and
    molecular components would open up major opportunities. However, electron microscopy
    (EM) provides nanometre-scale resolution required for full <jats:italic>in-silico</jats:italic>
    reconstruction<jats:sup>1–5</jats:sup>, yet is limited to fixed specimens and
    static representations. Light microscopy allows live observation, with super-resolution
    approaches<jats:sup>6–12</jats:sup> facilitating nanoscale visualization, but
    comprehensive 3D-reconstruction of living brain tissue has been hindered by tissue
    photo-burden, photobleaching, insufficient 3D-resolution, and inadequate signal-to-noise
    ratio (SNR). Here we demonstrate saturated reconstruction of living brain tissue.
    We developed an integrated imaging and analysis technology, adapting stimulated
    emission depletion (STED) microscopy<jats:sup>6,13</jats:sup> in extracellularly
    labelled tissue<jats:sup>14</jats:sup> for high SNR and near-isotropic resolution.
    Centrally, a two-stage deep-learning approach leveraged previously obtained information
    on sample structure to drastically reduce photo-burden and enable automated volumetric
    reconstruction down to single synapse level. Live reconstruction provides unbiased
    analysis of tissue architecture across time in relation to functional activity
    and targeted activation, and contextual understanding of molecular labelling.
    This adoptable technology will facilitate novel insights into the dynamic functional
    architecture of living brain tissue.
article_processing_charge: No
author:
- first_name: Philipp
  full_name: Velicky, Philipp
  id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
  last_name: Velicky
  orcid: 0000-0002-2340-7431
- first_name: Eder
  full_name: Miguel Villalba, Eder
  id: 3FB91342-F248-11E8-B48F-1D18A9856A87
  last_name: Miguel Villalba
  orcid: 0000-0001-5665-0430
- first_name: Julia M
  full_name: Michalska, Julia M
  id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
  last_name: Michalska
  orcid: 0000-0003-3862-1235
- first_name: Donglai
  full_name: Wei, Donglai
  last_name: Wei
- first_name: Zudi
  full_name: Lin, Zudi
  last_name: Lin
- first_name: Jake
  full_name: Watson, Jake
  id: 63836096-4690-11EA-BD4E-32803DDC885E
  last_name: Watson
  orcid: 0000-0002-8698-3823
- first_name: Jakob
  full_name: Troidl, Jakob
  last_name: Troidl
- first_name: Johanna
  full_name: Beyer, Johanna
  last_name: Beyer
- first_name: Yoav
  full_name: Ben Simon, Yoav
  id: 43DF3136-F248-11E8-B48F-1D18A9856A87
  last_name: Ben Simon
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Wiebke
  full_name: Jahr, Wiebke
  id: 425C1CE8-F248-11E8-B48F-1D18A9856A87
  last_name: Jahr
  orcid: 0000-0003-0201-2315
- first_name: Alban
  full_name: Cenameri, Alban
  id: 9ac8f577-2357-11eb-997a-e566c5550886
  last_name: Cenameri
- first_name: Johannes
  full_name: Broichhagen, Johannes
  last_name: Broichhagen
- first_name: Seth G. N.
  full_name: Grant, Seth G. N.
  last_name: Grant
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Hanspeter
  full_name: Pfister, Hanspeter
  last_name: Pfister
- first_name: Bernd
  full_name: Bickel, Bernd
  id: 49876194-F248-11E8-B48F-1D18A9856A87
  last_name: Bickel
  orcid: 0000-0001-6511-9385
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
citation:
  ama: Velicky P, Miguel Villalba E, Michalska JM, et al. Saturated reconstruction
    of living brain tissue. <i>bioRxiv</i>. doi:<a href="https://doi.org/10.1101/2022.03.16.484431">10.1101/2022.03.16.484431</a>
  apa: Velicky, P., Miguel Villalba, E., Michalska, J. M., Wei, D., Lin, Z., Watson,
    J., … Danzl, J. G. (n.d.). Saturated reconstruction of living brain tissue. <i>bioRxiv</i>.
    Cold Spring Harbor Laboratory. <a href="https://doi.org/10.1101/2022.03.16.484431">https://doi.org/10.1101/2022.03.16.484431</a>
  chicago: Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Donglai Wei,
    Zudi Lin, Jake Watson, Jakob Troidl, et al. “Saturated Reconstruction of Living
    Brain Tissue.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href="https://doi.org/10.1101/2022.03.16.484431">https://doi.org/10.1101/2022.03.16.484431</a>.
  ieee: P. Velicky <i>et al.</i>, “Saturated reconstruction of living brain tissue,”
    <i>bioRxiv</i>. Cold Spring Harbor Laboratory.
  ista: Velicky P, Miguel Villalba E, Michalska JM, Wei D, Lin Z, Watson J, Troidl
    J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN,
    Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. Saturated reconstruction
    of living brain tissue. bioRxiv, <a href="https://doi.org/10.1101/2022.03.16.484431">10.1101/2022.03.16.484431</a>.
  mla: Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.”
    <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href="https://doi.org/10.1101/2022.03.16.484431">10.1101/2022.03.16.484431</a>.
  short: P. Velicky, E. Miguel Villalba, J.M. Michalska, D. Wei, Z. Lin, J. Watson,
    J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen,
    S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, BioRxiv
    (n.d.).
corr_author: '1'
date_created: 2022-08-23T11:07:59Z
date_published: 2022-05-09T00:00:00Z
date_updated: 2026-06-07T22:30:35Z
day: '09'
department:
- _id: PeJo
- _id: GaNo
- _id: BeBi
- _id: JoDa
doi: 10.1101/2022.03.16.484431
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2022.03.16.484431
month: '05'
oa: 1
oa_version: Preprint
publication: bioRxiv
publication_status: draft
publisher: Cold Spring Harbor Laboratory
related_material:
  record:
  - id: '13267'
    relation: later_version
    status: public
  - id: '12470'
    relation: dissertation_contains
    status: public
status: public
title: Saturated reconstruction of living brain tissue
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...
---
_id: '11950'
abstract:
- lang: eng
  text: Mapping the complex and dense arrangement of cells and their connectivity
    in brain tissue demands nanoscale spatial resolution imaging. Super-resolution
    optical microscopy excels at visualizing specific molecules and individual cells
    but fails to provide tissue context. Here we developed Comprehensive Analysis
    of Tissues across Scales (CATS), a technology to densely map brain tissue architecture
    from millimeter regional to nanoscopic synaptic scales in diverse chemically fixed
    brain preparations, including rodent and human. CATS leverages fixation-compatible
    extracellular labeling and advanced optical readout, in particular stimulated-emission
    depletion and expansion microscopy, to comprehensively delineate cellular structures.
    It enables 3D-reconstructing single synapses and mapping synaptic connectivity
    by identification and tailored analysis of putative synaptic cleft regions. Applying
    CATS to the hippocampal mossy fiber circuitry, we demonstrate its power to reveal
    the system’s molecularly informed ultrastructure across spatial scales and assess
    local connectivity by reconstructing and quantifying the synaptic input and output
    structure of identified neurons.
article_processing_charge: No
author:
- first_name: Julia M
  full_name: Michalska, Julia M
  id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
  last_name: Michalska
  orcid: 0000-0003-3862-1235
- first_name: Julia
  full_name: Lyudchik, Julia
  id: 46E28B80-F248-11E8-B48F-1D18A9856A87
  last_name: Lyudchik
- first_name: Philipp
  full_name: Velicky, Philipp
  id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
  last_name: Velicky
  orcid: 0000-0002-2340-7431
- first_name: Hana
  full_name: Korinkova, Hana
  id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed
  last_name: Korinkova
- first_name: Jake
  full_name: Watson, Jake
  id: 63836096-4690-11EA-BD4E-32803DDC885E
  last_name: Watson
  orcid: 0000-0002-8698-3823
- first_name: Alban
  full_name: Cenameri, Alban
  id: 9ac8f577-2357-11eb-997a-e566c5550886
  last_name: Cenameri
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Alessandro
  full_name: Venturino, Alessandro
  id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
  last_name: Venturino
  orcid: 0000-0003-2356-9403
- first_name: Karl
  full_name: Roessler, Karl
  last_name: Roessler
- first_name: Thomas
  full_name: Czech, Thomas
  last_name: Czech
- first_name: Sandra
  full_name: Siegert, Sandra
  id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
  last_name: Siegert
  orcid: 0000-0001-8635-0877
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
citation:
  ama: Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture
    across scales with super-resolution light microscopy. <i>bioRxiv</i>. doi:<a href="https://doi.org/10.1101/2022.08.17.504272">10.1101/2022.08.17.504272</a>
  apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri,
    A., … Danzl, J. G. (n.d.). Uncovering brain tissue architecture across scales
    with super-resolution light microscopy. <i>bioRxiv</i>. Cold Spring Harbor Laboratory.
    <a href="https://doi.org/10.1101/2022.08.17.504272">https://doi.org/10.1101/2022.08.17.504272</a>
  chicago: Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake
    Watson, Alban Cenameri, Christoph M Sommer, et al. “Uncovering Brain Tissue Architecture
    across Scales with Super-Resolution Light Microscopy.” <i>BioRxiv</i>. Cold Spring
    Harbor Laboratory, n.d. <a href="https://doi.org/10.1101/2022.08.17.504272">https://doi.org/10.1101/2022.08.17.504272</a>.
  ieee: J. M. Michalska <i>et al.</i>, “Uncovering brain tissue architecture across
    scales with super-resolution light microscopy,” <i>bioRxiv</i>. Cold Spring Harbor
    Laboratory.
  ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer
    CM, Venturino A, Roessler K, Czech T, Siegert S, Novarino G, Jonas PM, Danzl JG.
    Uncovering brain tissue architecture across scales with super-resolution light
    microscopy. bioRxiv, <a href="https://doi.org/10.1101/2022.08.17.504272">10.1101/2022.08.17.504272</a>.
  mla: Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales
    with Super-Resolution Light Microscopy.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory,
    doi:<a href="https://doi.org/10.1101/2022.08.17.504272">10.1101/2022.08.17.504272</a>.
  short: J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri,
    C.M. Sommer, A. Venturino, K. Roessler, T. Czech, S. Siegert, G. Novarino, P.M.
    Jonas, J.G. Danzl, BioRxiv (n.d.).
corr_author: '1'
date_created: 2022-08-24T08:24:52Z
date_published: 2022-08-18T00:00:00Z
date_updated: 2026-06-07T22:30:35Z
day: '18'
department:
- _id: SaSi
- _id: GaNo
- _id: PeJo
- _id: JoDa
doi: 10.1101/2022.08.17.504272
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2022.08.17.504272
month: '08'
oa: 1
oa_version: Preprint
publication: bioRxiv
publication_status: draft
publisher: Cold Spring Harbor Laboratory
related_material:
  record:
  - id: '12470'
    relation: dissertation_contains
    status: public
status: public
title: Uncovering brain tissue architecture across scales with super-resolution light
  microscopy
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...
---
_id: '15273'
abstract:
- lang: eng
  text: Synapses of glutamatergic mossy fibers (MFs) onto cerebellar unipolar brush
    cells (UBCs) generate slow excitatory (ON) or inhibitory (OFF) postsynaptic responses
    dependent on the complement of glutamate receptors expressed on the UBC’s large
    dendritic brush. Using mouse brain slice recording and computational modeling
    of synaptic transmission, we found that substantial glutamate is maintained in
    the UBC synaptic cleft, sufficient to modify spontaneous firing in OFF UBCs and
    tonically desensitize AMPARs of ON UBCs. The source of this ambient glutamate
    was spontaneous, spike-independent exocytosis from the MF terminal, and its level
    was dependent on activity of glutamate transporters EAAT1–2. Increasing levels
    of ambient glutamate shifted the polarity of evoked synaptic responses in ON UBCs
    and altered the phase of responses to in vivo-like synaptic activity. Unlike classical
    fast synapses, receptors at the UBC synapse are virtually always exposed to a
    significant level of glutamate, which varies in a graded manner during transmission.
article_number: e63819
article_processing_charge: Yes
article_type: original
author:
- first_name: Timothy S
  full_name: Balmer, Timothy S
  last_name: Balmer
- first_name: Carolina
  full_name: Borges Merjane, Carolina
  id: 4305C450-F248-11E8-B48F-1D18A9856A87
  last_name: Borges Merjane
  orcid: 0000-0003-0005-401X
- first_name: Laurence O
  full_name: Trussell, Laurence O
  last_name: Trussell
citation:
  ama: Balmer TS, Borges Merjane C, Trussell LO. Incomplete removal of extracellular
    glutamate controls synaptic transmission and integration at a cerebellar synapse.
    <i>eLife</i>. 2021;10. doi:<a href="https://doi.org/10.7554/elife.63819">10.7554/elife.63819</a>
  apa: Balmer, T. S., Borges Merjane, C., &#38; Trussell, L. O. (2021). Incomplete
    removal of extracellular glutamate controls synaptic transmission and integration
    at a cerebellar synapse. <i>ELife</i>. eLife Sciences Publications. <a href="https://doi.org/10.7554/elife.63819">https://doi.org/10.7554/elife.63819</a>
  chicago: Balmer, Timothy S, Carolina Borges Merjane, and Laurence O Trussell. “Incomplete
    Removal of Extracellular Glutamate Controls Synaptic Transmission and Integration
    at a Cerebellar Synapse.” <i>ELife</i>. eLife Sciences Publications, 2021. <a
    href="https://doi.org/10.7554/elife.63819">https://doi.org/10.7554/elife.63819</a>.
  ieee: T. S. Balmer, C. Borges Merjane, and L. O. Trussell, “Incomplete removal of
    extracellular glutamate controls synaptic transmission and integration at a cerebellar
    synapse,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.
  ista: Balmer TS, Borges Merjane C, Trussell LO. 2021. Incomplete removal of extracellular
    glutamate controls synaptic transmission and integration at a cerebellar synapse.
    eLife. 10, e63819.
  mla: Balmer, Timothy S., et al. “Incomplete Removal of Extracellular Glutamate Controls
    Synaptic Transmission and Integration at a Cerebellar Synapse.” <i>ELife</i>,
    vol. 10, e63819, eLife Sciences Publications, 2021, doi:<a href="https://doi.org/10.7554/elife.63819">10.7554/elife.63819</a>.
  short: T.S. Balmer, C. Borges Merjane, L.O. Trussell, ELife 10 (2021).
date_created: 2024-04-03T07:58:11Z
date_published: 2021-02-22T00:00:00Z
date_updated: 2024-04-09T11:15:01Z
day: '22'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.7554/elife.63819
external_id:
  pmid:
  - '33616036'
file:
- access_level: open_access
  checksum: bbd4de2e54b7fbc11fba14f59e87fe3f
  content_type: application/pdf
  creator: dernst
  date_created: 2024-04-09T11:13:07Z
  date_updated: 2024-04-09T11:13:07Z
  file_id: '15307'
  file_name: 2021_eLife_Balmer.pdf
  file_size: 6997954
  relation: main_file
  success: 1
file_date_updated: 2024-04-09T11:13:07Z
has_accepted_license: '1'
intvolume: '        10'
keyword:
- General Immunology and Microbiology
- General Biochemistry
- Genetics and Molecular Biology
- General Medicine
- General Neuroscience
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
publication: eLife
publication_identifier:
  issn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
status: public
title: Incomplete removal of extracellular glutamate controls synaptic transmission
  and integration at a cerebellar synapse
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 10
year: '2021'
...
---
_id: '9329'
abstract:
- lang: eng
  text: "Background: To understand information coding in single neurons, it is necessary
    to analyze subthreshold synaptic events, action potentials (APs), and their interrelation
    in different behavioral states. However, detecting excitatory postsynaptic potentials
    (EPSPs) or currents (EPSCs) in behaving animals remains challenging, because of
    unfavorable signal-to-noise ratio, high frequency, fluctuating amplitude, and
    variable time course of synaptic events.\r\nNew method: We developed a method
    for synaptic event detection, termed MOD (Machine-learning Optimal-filtering Detection-procedure),
    which combines concepts of supervised machine learning and optimal Wiener filtering.
    Experts were asked to manually score short epochs of data. The algorithm was trained
    to obtain the optimal filter coefficients of a Wiener filter and the optimal detection
    threshold. Scored and unscored data were then processed with the optimal filter,
    and events were detected as peaks above threshold.\r\nResults: We challenged MOD
    with EPSP traces in vivo in mice during spatial navigation and EPSC traces in
    vitro in slices under conditions of enhanced transmitter release. The area under
    the curve (AUC) of the receiver operating characteristics (ROC) curve was, on
    average, 0.894 for in vivo and 0.969 for in vitro data sets, indicating high detection
    accuracy and efficiency.\r\nComparison with existing methods: When benchmarked
    using a (1 − AUC)−1 metric, MOD outperformed previous methods (template-fit, deconvolution,
    and Bayesian methods) by an average factor of 3.13 for in vivo data sets, but
    showed comparable (template-fit, deconvolution) or higher (Bayesian) computational
    efficacy.\r\nConclusions: MOD may become an important new tool for large-scale,
    real-time analysis of synaptic activity."
acknowledged_ssus:
- _id: SSU
acknowledgement: This project has received funding from the European Research Council
  (ERC) under the European Union’s Horizon 2020 research and innovation programme
  (grant agreement number 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen
  Forschung (Z 312-B27, Wittgenstein award to P.J.). We thank Drs. Jozsef Csicsvari,
  Christoph Lampert, and Federico Stella for critically reading previous manuscript
  versions. We are also grateful to Drs. Josh Merel and Ben Shababo for their help
  with applying the Bayesian detection method to our data. We also thank Florian Marr
  for technical assistance, Eleftheria Kralli-Beller for manuscript editing, and the
  Scientific Service Units of IST Austria for efficient support.
article_number: '109125'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Xiaomin
  full_name: Zhang, Xiaomin
  id: 423EC9C2-F248-11E8-B48F-1D18A9856A87
  last_name: Zhang
- first_name: Alois
  full_name: Schlögl, Alois
  id: 45BF87EE-F248-11E8-B48F-1D18A9856A87
  last_name: Schlögl
  orcid: 0000-0002-5621-8100
- first_name: David H
  full_name: Vandael, David H
  id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87
  last_name: Vandael
  orcid: 0000-0001-7577-1676
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
citation:
  ama: 'Zhang X, Schlögl A, Vandael DH, Jonas PM. MOD: A novel machine-learning optimal-filtering
    method for accurate and efficient detection of subthreshold synaptic events in
    vivo. <i>Journal of Neuroscience Methods</i>. 2021;357(6). doi:<a href="https://doi.org/10.1016/j.jneumeth.2021.109125">10.1016/j.jneumeth.2021.109125</a>'
  apa: 'Zhang, X., Schlögl, A., Vandael, D. H., &#38; Jonas, P. M. (2021). MOD: A
    novel machine-learning optimal-filtering method for accurate and efficient detection
    of subthreshold synaptic events in vivo. <i>Journal of Neuroscience Methods</i>.
    Elsevier. <a href="https://doi.org/10.1016/j.jneumeth.2021.109125">https://doi.org/10.1016/j.jneumeth.2021.109125</a>'
  chicago: 'Zhang, Xiaomin, Alois Schlögl, David H Vandael, and Peter M Jonas. “MOD:
    A Novel Machine-Learning Optimal-Filtering Method for Accurate and Efficient Detection
    of Subthreshold Synaptic Events in Vivo.” <i>Journal of Neuroscience Methods</i>.
    Elsevier, 2021. <a href="https://doi.org/10.1016/j.jneumeth.2021.109125">https://doi.org/10.1016/j.jneumeth.2021.109125</a>.'
  ieee: 'X. Zhang, A. Schlögl, D. H. Vandael, and P. M. Jonas, “MOD: A novel machine-learning
    optimal-filtering method for accurate and efficient detection of subthreshold
    synaptic events in vivo,” <i>Journal of Neuroscience Methods</i>, vol. 357, no.
    6. Elsevier, 2021.'
  ista: 'Zhang X, Schlögl A, Vandael DH, Jonas PM. 2021. MOD: A novel machine-learning
    optimal-filtering method for accurate and efficient detection of subthreshold
    synaptic events in vivo. Journal of Neuroscience Methods. 357(6), 109125.'
  mla: 'Zhang, Xiaomin, et al. “MOD: A Novel Machine-Learning Optimal-Filtering Method
    for Accurate and Efficient Detection of Subthreshold Synaptic Events in Vivo.”
    <i>Journal of Neuroscience Methods</i>, vol. 357, no. 6, 109125, Elsevier, 2021,
    doi:<a href="https://doi.org/10.1016/j.jneumeth.2021.109125">10.1016/j.jneumeth.2021.109125</a>.'
  short: X. Zhang, A. Schlögl, D.H. Vandael, P.M. Jonas, Journal of Neuroscience Methods
    357 (2021).
date_created: 2021-04-18T22:01:39Z
date_published: 2021-03-09T00:00:00Z
date_updated: 2025-06-12T06:39:15Z
day: '09'
ddc:
- '570'
department:
- _id: PeJo
- _id: ScienComp
doi: 10.1016/j.jneumeth.2021.109125
ec_funded: 1
external_id:
  isi:
  - '000661088500005'
  pmid:
  - '33711356'
file:
- access_level: open_access
  checksum: 2a5800d91b96d08b525e17319dcd5e44
  content_type: application/pdf
  creator: dernst
  date_created: 2021-04-19T08:30:22Z
  date_updated: 2021-04-19T08:30:22Z
  file_id: '9339'
  file_name: 2021_JourNeuroscienceMeth_Zhang.pdf
  file_size: 6924738
  relation: main_file
  success: 1
file_date_updated: 2021-04-19T08:30:22Z
has_accepted_license: '1'
intvolume: '       357'
isi: 1
issue: '6'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z00312
  name: Synaptic communication in neuronal microcircuits
publication: Journal of Neuroscience Methods
publication_identifier:
  eissn:
  - 1872-678X
  issn:
  - 0165-0270
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'MOD: A novel machine-learning optimal-filtering method for accurate and efficient
  detection of subthreshold synaptic events in vivo'
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 357
year: '2021'
...
---
_id: '9549'
abstract:
- lang: eng
  text: 'AMPA receptors (AMPARs) mediate the majority of excitatory transmission in
    the brain and enable the synaptic plasticity that underlies learning1. A diverse
    array of AMPAR signalling complexes are established by receptor auxiliary subunits,
    which associate with the AMPAR in various combinations to modulate trafficking,
    gating and synaptic strength2. However, their mechanisms of action are poorly
    understood. Here we determine cryo-electron microscopy structures of the heteromeric
    GluA1–GluA2 receptor assembled with both TARP-γ8 and CNIH2, the predominant AMPAR
    complex in the forebrain, in both resting and active states. Two TARP-γ8 and two
    CNIH2 subunits insert at distinct sites beneath the ligand-binding domains of
    the receptor, with site-specific lipids shaping each interaction and affecting
    the gating regulation of the AMPARs. Activation of the receptor leads to asymmetry
    between GluA1 and GluA2 along the ion conduction path and an outward expansion
    of the channel triggers counter-rotations of both auxiliary subunit pairs, promoting
    the active-state conformation. In addition, both TARP-γ8 and CNIH2 pivot towards
    the pore exit upon activation, extending their reach for cytoplasmic receptor
    elements. CNIH2 achieves this through its uniquely extended M2 helix, which has
    transformed this endoplasmic reticulum-export factor into a powerful AMPAR modulator
    that is capable of providing hippocampal pyramidal neurons with their integrative
    synaptic properties. '
acknowledgement: We thank members of the Greger laboratory, B. Herguedas, J. Krieger
  and J.-N. Dohrke for comments on the manuscript; J. Krieger and J.-N. Dohrke for
  discussion, J. Krieger for help with the normal mode analysis, B. Köhegyi for help
  with cryo-EM imaging, V. Chang and K. Suzuki for helping to generate the CNIH2-1D4-HA
  stable cell line, M. Carvalho for assistance at early stages of this project, the
  LMB scientific computing and the cryo-EM facility for support, P. Emsley for help
  with model building, T. Nakane for helpful comments with RELION 3.1 and R. Warshamanage
  for helping with EMDA cryo-EM-map processing. We acknowledge the Diamond Light Source
  for access and support of the Cryo-EM facilities at the UK national electron bio10
  imaging centre (eBIC), proposal EM17434, funded by the Wellcome Trust, MRC and BBSRC.
  This work was supported by grants from the Medical Research Council, as part of
  United Kingdom Research and Innovation (also known as UK Research and Innovation)
  (MC_U105174197) and BBSRC (BB/N002113/1) to I.H.G.
article_processing_charge: No
article_type: original
author:
- first_name: Danyang
  full_name: Zhang, Danyang
  last_name: Zhang
- first_name: Jake
  full_name: Watson, Jake
  id: 63836096-4690-11EA-BD4E-32803DDC885E
  last_name: Watson
  orcid: 0000-0002-8698-3823
- first_name: Peter M.
  full_name: Matthews, Peter M.
  last_name: Matthews
- first_name: Ondrej
  full_name: Cais, Ondrej
  last_name: Cais
- first_name: Ingo H.
  full_name: Greger, Ingo H.
  last_name: Greger
citation:
  ama: Zhang D, Watson J, Matthews PM, Cais O, Greger IH. Gating and modulation of
    a hetero-octameric AMPA glutamate receptor. <i>Nature</i>. 2021;594:454-458. doi:<a
    href="https://doi.org/10.1038/s41586-021-03613-0">10.1038/s41586-021-03613-0</a>
  apa: Zhang, D., Watson, J., Matthews, P. M., Cais, O., &#38; Greger, I. H. (2021).
    Gating and modulation of a hetero-octameric AMPA glutamate receptor. <i>Nature</i>.
    Springer Nature. <a href="https://doi.org/10.1038/s41586-021-03613-0">https://doi.org/10.1038/s41586-021-03613-0</a>
  chicago: Zhang, Danyang, Jake Watson, Peter M. Matthews, Ondrej Cais, and Ingo H.
    Greger. “Gating and Modulation of a Hetero-Octameric AMPA Glutamate Receptor.”
    <i>Nature</i>. Springer Nature, 2021. <a href="https://doi.org/10.1038/s41586-021-03613-0">https://doi.org/10.1038/s41586-021-03613-0</a>.
  ieee: D. Zhang, J. Watson, P. M. Matthews, O. Cais, and I. H. Greger, “Gating and
    modulation of a hetero-octameric AMPA glutamate receptor,” <i>Nature</i>, vol.
    594. Springer Nature, pp. 454–458, 2021.
  ista: Zhang D, Watson J, Matthews PM, Cais O, Greger IH. 2021. Gating and modulation
    of a hetero-octameric AMPA glutamate receptor. Nature. 594, 454–458.
  mla: Zhang, Danyang, et al. “Gating and Modulation of a Hetero-Octameric AMPA Glutamate
    Receptor.” <i>Nature</i>, vol. 594, Springer Nature, 2021, pp. 454–58, doi:<a
    href="https://doi.org/10.1038/s41586-021-03613-0">10.1038/s41586-021-03613-0</a>.
  short: D. Zhang, J. Watson, P.M. Matthews, O. Cais, I.H. Greger, Nature 594 (2021)
    454–458.
date_created: 2021-06-13T22:01:33Z
date_published: 2021-06-02T00:00:00Z
date_updated: 2023-08-08T13:59:51Z
day: '02'
department:
- _id: PeJo
doi: 10.1038/s41586-021-03613-0
external_id:
  isi:
  - '000657238100003'
  pmid:
  - '34079129'
intvolume: '       594'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1038/s41586-021-03613-0
month: '06'
oa: 1
oa_version: Published Version
page: 454-458
pmid: 1
publication: Nature
publication_identifier:
  eissn:
  - 1476-4687
  issn:
  - 0028-0836
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Gating and modulation of a hetero-octameric AMPA glutamate receptor
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 594
year: '2021'
...
---
OA_place: publisher
OA_type: gold
_id: '9778'
abstract:
- lang: eng
  text: The hippocampal mossy fiber synapse is a key synapse of the trisynaptic circuit.
    Post-tetanic potentiation (PTP) is the most powerful form of plasticity at this
    synaptic connection. It is widely believed that mossy fiber PTP is an entirely
    presynaptic phenomenon, implying that PTP induction is input-specific, and requires
    neither activity of multiple inputs nor stimulation of postsynaptic neurons. To
    directly test cooperativity and associativity, we made paired recordings between
    single mossy fiber terminals and postsynaptic CA3 pyramidal neurons in rat brain
    slices. By stimulating non-overlapping mossy fiber inputs converging onto single
    CA3 neurons, we confirm that PTP is input-specific and non-cooperative. Unexpectedly,
    mossy fiber PTP exhibits anti-associative induction properties. EPSCs show only
    minimal PTP after combined pre- and postsynaptic high-frequency stimulation with
    intact postsynaptic Ca2+ signaling, but marked PTP in the absence of postsynaptic
    spiking and after suppression of postsynaptic Ca2+ signaling (10 mM EGTA). PTP
    is largely recovered by inhibitors of voltage-gated R- and L-type Ca2+ channels,
    group II mGluRs, and vacuolar-type H+-ATPase, suggesting the involvement of retrograde
    vesicular glutamate signaling. Transsynaptic regulation of PTP extends the repertoire
    of synaptic computations, implementing a brake on mossy fiber detonation and a
    “smart teacher” function of hippocampal mossy fiber synapses.
acknowledged_ssus:
- _id: SSU
acknowledgement: We thank Drs. Carolina Borges-Merjane and Jose Guzman for critically
  reading the manuscript, and Pablo Castillo for discussions. We are grateful to Alois
  Schlögl for help with analysis, Florian Marr for excellent technical assistance
  and cell reconstruction, Christina Altmutter for technical help, Eleftheria Kralli-Beller
  for manuscript editing, and the Scientific Service Units of IST Austria for support.
  This project received funding from the European Research Council (ERC) under the
  European Union’s Horizon 2020 research and innovation program (grant agreement No
  692692) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27,
  Wittgenstein award), both to P.J.
article_number: '2912'
article_processing_charge: Yes
article_type: original
author:
- first_name: David H
  full_name: Vandael, David H
  id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87
  last_name: Vandael
  orcid: 0000-0001-7577-1676
- first_name: Yuji
  full_name: Okamoto, Yuji
  id: 3337E116-F248-11E8-B48F-1D18A9856A87
  last_name: Okamoto
  orcid: 0000-0003-0408-6094
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
citation:
  ama: Vandael DH, Okamoto Y, Jonas PM. Transsynaptic modulation of presynaptic short-term
    plasticity in hippocampal mossy fiber synapses. <i>Nature Communications</i>.
    2021;12(1). doi:<a href="https://doi.org/10.1038/s41467-021-23153-5">10.1038/s41467-021-23153-5</a>
  apa: Vandael, D. H., Okamoto, Y., &#38; Jonas, P. M. (2021). Transsynaptic modulation
    of presynaptic short-term plasticity in hippocampal mossy fiber synapses. <i>Nature
    Communications</i>. Springer. <a href="https://doi.org/10.1038/s41467-021-23153-5">https://doi.org/10.1038/s41467-021-23153-5</a>
  chicago: Vandael, David H, Yuji Okamoto, and Peter M Jonas. “Transsynaptic Modulation
    of Presynaptic Short-Term Plasticity in Hippocampal Mossy Fiber Synapses.” <i>Nature
    Communications</i>. Springer, 2021. <a href="https://doi.org/10.1038/s41467-021-23153-5">https://doi.org/10.1038/s41467-021-23153-5</a>.
  ieee: D. H. Vandael, Y. Okamoto, and P. M. Jonas, “Transsynaptic modulation of presynaptic
    short-term plasticity in hippocampal mossy fiber synapses,” <i>Nature Communications</i>,
    vol. 12, no. 1. Springer, 2021.
  ista: Vandael DH, Okamoto Y, Jonas PM. 2021. Transsynaptic modulation of presynaptic
    short-term plasticity in hippocampal mossy fiber synapses. Nature Communications.
    12(1), 2912.
  mla: Vandael, David H., et al. “Transsynaptic Modulation of Presynaptic Short-Term
    Plasticity in Hippocampal Mossy Fiber Synapses.” <i>Nature Communications</i>,
    vol. 12, no. 1, 2912, Springer, 2021, doi:<a href="https://doi.org/10.1038/s41467-021-23153-5">10.1038/s41467-021-23153-5</a>.
  short: D.H. Vandael, Y. Okamoto, P.M. Jonas, Nature Communications 12 (2021).
corr_author: '1'
date_created: 2021-08-06T07:22:55Z
date_published: 2021-05-18T00:00:00Z
date_updated: 2025-06-12T06:28:45Z
day: '18'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1038/s41467-021-23153-5
ec_funded: 1
external_id:
  isi:
  - '000655481800014'
  pmid:
  - '34006874'
file:
- access_level: open_access
  checksum: 6036a8cdae95e1707c2a04d54e325ff4
  content_type: application/pdf
  creator: kschuh
  date_created: 2021-12-17T11:34:50Z
  date_updated: 2021-12-17T11:34:50Z
  file_id: '10563'
  file_name: 2021_NatureCommunications_Vandael.pdf
  file_size: 3108845
  relation: main_file
  success: 1
file_date_updated: 2021-12-17T11:34:50Z
has_accepted_license: '1'
intvolume: '        12'
isi: 1
issue: '1'
keyword:
- general physics and astronomy
- general biochemistry
- genetics and molecular biology
- general chemistry
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z00312
  name: Synaptic communication in neuronal microcircuits
publication: Nature Communications
publication_identifier:
  issn:
  - 2041-1723
publication_status: published
publisher: Springer
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/synaptic-transmission-not-a-one-way-street/
scopus_import: '1'
status: public
title: Transsynaptic modulation of presynaptic short-term plasticity in hippocampal
  mossy fiber synapses
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 12
year: '2021'
...
---
_id: '9985'
abstract:
- lang: eng
  text: AMPA receptor (AMPAR) abundance and positioning at excitatory synapses regulates
    the strength of transmission. Changes in AMPAR localisation can enact synaptic
    plasticity, allowing long-term information storage, and is therefore tightly controlled.
    Multiple mechanisms regulating AMPAR synaptic anchoring have been described, but
    with limited coherence or comparison between reports, our understanding of this
    process is unclear. Here, combining synaptic recordings from mouse hippocampal
    slices and super-resolution imaging in dissociated cultures, we compare the contributions
    of three AMPAR interaction domains controlling transmission at hippocampal CA1
    synapses. We show that the AMPAR C-termini play only a modulatory role, whereas
    the extracellular N-terminal domain (NTD) and PDZ interactions of the auxiliary
    subunit TARP γ8 are both crucial, and each is sufficient to maintain transmission.
    Our data support a model in which γ8 accumulates AMPARs at the postsynaptic density,
    where the NTD further tunes their positioning. This interplay between cytosolic
    (TARP γ8) and synaptic cleft (NTD) interactions provides versatility to regulate
    synaptic transmission and plasticity.
acknowledgement: The authors are very grateful to Andrew Penn for advice and discussions
  on surface receptor labelling in slice tissue, dissociated culture transfection,
  and for providing tdTomato and BirAER expression plasmids. This work would not have
  been possible without support from the Biological Services teams at both the Laboratory
  of Molecular Biology and Ares facilities. We are also very grateful to Nick Barry
  and Jerome Boulanger of the LMB Light Microscopy facility for support with confocal
  and STORM imaging and analysis, Junichi Takagi for providing scFv-Clasp expression
  constructs, Veronica Chang for assistance with scFv-Clasp protein production, and
  Nejc Kejzar for assistance with cluster analysis. We would like to thank Teru Nakagawa
  and Ole Paulsen for critical reading of the manuscript and constructive feedback.
  This work was supported by grants from the Medical Research Council (MC_U105174197)
  and BBSRC (BB/N002113/1).
article_number: '5083'
article_processing_charge: Yes
article_type: original
author:
- first_name: Jake
  full_name: Watson, Jake
  id: 63836096-4690-11EA-BD4E-32803DDC885E
  last_name: Watson
  orcid: 0000-0002-8698-3823
- first_name: Alexandra
  full_name: Pinggera, Alexandra
  last_name: Pinggera
- first_name: Hinze
  full_name: Ho, Hinze
  last_name: Ho
- first_name: Ingo H.
  full_name: Greger, Ingo H.
  last_name: Greger
citation:
  ama: Watson J, Pinggera A, Ho H, Greger IH. AMPA receptor anchoring at CA1 synapses
    is determined by N-terminal domain and TARP γ8 interactions. <i>Nature Communications</i>.
    2021;12(1). doi:<a href="https://doi.org/10.1038/s41467-021-25281-4">10.1038/s41467-021-25281-4</a>
  apa: Watson, J., Pinggera, A., Ho, H., &#38; Greger, I. H. (2021). AMPA receptor
    anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions.
    <i>Nature Communications</i>. Nature Publishing Group. <a href="https://doi.org/10.1038/s41467-021-25281-4">https://doi.org/10.1038/s41467-021-25281-4</a>
  chicago: Watson, Jake, Alexandra Pinggera, Hinze Ho, and Ingo H. Greger. “AMPA Receptor
    Anchoring at CA1 Synapses Is Determined by N-Terminal Domain and TARP Γ8 Interactions.”
    <i>Nature Communications</i>. Nature Publishing Group, 2021. <a href="https://doi.org/10.1038/s41467-021-25281-4">https://doi.org/10.1038/s41467-021-25281-4</a>.
  ieee: J. Watson, A. Pinggera, H. Ho, and I. H. Greger, “AMPA receptor anchoring
    at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions,”
    <i>Nature Communications</i>, vol. 12, no. 1. Nature Publishing Group, 2021.
  ista: Watson J, Pinggera A, Ho H, Greger IH. 2021. AMPA receptor anchoring at CA1
    synapses is determined by N-terminal domain and TARP γ8 interactions. Nature Communications.
    12(1), 5083.
  mla: Watson, Jake, et al. “AMPA Receptor Anchoring at CA1 Synapses Is Determined
    by N-Terminal Domain and TARP Γ8 Interactions.” <i>Nature Communications</i>,
    vol. 12, no. 1, 5083, Nature Publishing Group, 2021, doi:<a href="https://doi.org/10.1038/s41467-021-25281-4">10.1038/s41467-021-25281-4</a>.
  short: J. Watson, A. Pinggera, H. Ho, I.H. Greger, Nature Communications 12 (2021).
date_created: 2021-09-05T22:01:23Z
date_published: 2021-08-23T00:00:00Z
date_updated: 2023-08-11T11:07:51Z
day: '23'
ddc:
- '612'
department:
- _id: PeJo
doi: 10.1038/s41467-021-25281-4
external_id:
  isi:
  - '000687672000006'
  pmid:
  - '34426577 '
file:
- access_level: open_access
  checksum: 1bf4f6a561f96bc426d754de9cb57710
  content_type: application/pdf
  creator: cchlebak
  date_created: 2021-09-08T12:57:06Z
  date_updated: 2021-09-08T12:57:06Z
  file_id: '9991'
  file_name: 2021_NatureCommunications_Watson.pdf
  file_size: 18310502
  relation: main_file
  success: 1
file_date_updated: 2021-09-08T12:57:06Z
has_accepted_license: '1'
intvolume: '        12'
isi: 1
issue: '1'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
publication: Nature Communications
publication_identifier:
  eissn:
  - 2041-1723
publication_status: published
publisher: Nature Publishing Group
quality_controlled: '1'
scopus_import: '1'
status: public
title: AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain
  and TARP γ8 interactions
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 12
year: '2021'
...
---
_id: '9438'
abstract:
- lang: eng
  text: Rigorous investigation of synaptic transmission requires analysis of unitary
    synaptic events by simultaneous recording from presynaptic terminals and postsynaptic
    target neurons. However, this has been achieved at only a limited number of model
    synapses, including the squid giant synapse and the mammalian calyx of Held. Cortical
    presynaptic terminals have been largely inaccessible to direct presynaptic recording,
    due to their small size. Here, we describe a protocol for improved subcellular
    patch-clamp recording in rat and mouse brain slices, with the synapse in a largely
    intact environment. Slice preparation takes ~2 h, recording ~3 h and post hoc
    morphological analysis 2 d. Single presynaptic hippocampal mossy fiber terminals
    are stimulated minimally invasively in the bouton-attached configuration, in which
    the cytoplasmic content remains unperturbed, or in the whole-bouton configuration,
    in which the cytoplasmic composition can be precisely controlled. Paired pre–postsynaptic
    recordings can be integrated with biocytin labeling and morphological analysis,
    allowing correlative investigation of synapse structure and function. Paired recordings
    can be obtained from mossy fiber terminals in slices from both rats and mice,
    implying applicability to genetically modified synapses. Paired recordings can
    also be performed together with axon tract stimulation or optogenetic activation,
    allowing comparison of unitary and compound synaptic events in the same target
    cell. Finally, paired recordings can be combined with spontaneous event analysis,
    permitting collection of miniature events generated at a single identified synapse.
    In conclusion, the subcellular patch-clamp techniques detailed here should facilitate
    analysis of biophysics, plasticity and circuit function of cortical synapses in
    the mammalian central nervous system.
acknowledged_ssus:
- _id: M-Shop
acknowledgement: This project received funding from the European Research Council
  (ERC) under the European Union’s Horizon 2020 research and innovation programme
  (grant agreement no. 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen
  Forschung (Z 312-B27, Wittgenstein award to P.J., V 739-B27 to C.B.M.). We are grateful
  to F. Marr and C. Altmutter for excellent technical assistance and cell reconstruction,
  E. Kralli-Beller for manuscript editing, and the Scientific Service Units of IST
  Austria, especially T. Asenov and Miba machine shop, for maximally efficient support.
article_processing_charge: No
article_type: original
author:
- first_name: David H
  full_name: Vandael, David H
  id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87
  last_name: Vandael
  orcid: 0000-0001-7577-1676
- first_name: Yuji
  full_name: Okamoto, Yuji
  id: 3337E116-F248-11E8-B48F-1D18A9856A87
  last_name: Okamoto
  orcid: 0000-0003-0408-6094
- first_name: Carolina
  full_name: Borges Merjane, Carolina
  id: 4305C450-F248-11E8-B48F-1D18A9856A87
  last_name: Borges Merjane
  orcid: 0000-0003-0005-401X
- first_name: Victor M
  full_name: Vargas Barroso, Victor M
  id: 2F55A9DE-F248-11E8-B48F-1D18A9856A87
  last_name: Vargas Barroso
- first_name: Benjamin
  full_name: Suter, Benjamin
  id: 4952F31E-F248-11E8-B48F-1D18A9856A87
  last_name: Suter
  orcid: 0000-0002-9885-6936
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
citation:
  ama: Vandael DH, Okamoto Y, Borges Merjane C, Vargas Barroso VM, Suter B, Jonas
    PM. Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous
    pre- and postsynaptic recording at cortical synapses. <i>Nature Protocols</i>.
    2021;16(6):2947–2967. doi:<a href="https://doi.org/10.1038/s41596-021-00526-0">10.1038/s41596-021-00526-0</a>
  apa: Vandael, D. H., Okamoto, Y., Borges Merjane, C., Vargas Barroso, V. M., Suter,
    B., &#38; Jonas, P. M. (2021). Subcellular patch-clamp techniques for single-bouton
    stimulation and simultaneous pre- and postsynaptic recording at cortical synapses.
    <i>Nature Protocols</i>. Springer Nature. <a href="https://doi.org/10.1038/s41596-021-00526-0">https://doi.org/10.1038/s41596-021-00526-0</a>
  chicago: Vandael, David H, Yuji Okamoto, Carolina Borges Merjane, Victor M Vargas
    Barroso, Benjamin Suter, and Peter M Jonas. “Subcellular Patch-Clamp Techniques
    for Single-Bouton Stimulation and Simultaneous Pre- and Postsynaptic Recording
    at Cortical Synapses.” <i>Nature Protocols</i>. Springer Nature, 2021. <a href="https://doi.org/10.1038/s41596-021-00526-0">https://doi.org/10.1038/s41596-021-00526-0</a>.
  ieee: D. H. Vandael, Y. Okamoto, C. Borges Merjane, V. M. Vargas Barroso, B. Suter,
    and P. M. Jonas, “Subcellular patch-clamp techniques for single-bouton stimulation
    and simultaneous pre- and postsynaptic recording at cortical synapses,” <i>Nature
    Protocols</i>, vol. 16, no. 6. Springer Nature, pp. 2947–2967, 2021.
  ista: Vandael DH, Okamoto Y, Borges Merjane C, Vargas Barroso VM, Suter B, Jonas
    PM. 2021. Subcellular patch-clamp techniques for single-bouton stimulation and
    simultaneous pre- and postsynaptic recording at cortical synapses. Nature Protocols.
    16(6), 2947–2967.
  mla: Vandael, David H., et al. “Subcellular Patch-Clamp Techniques for Single-Bouton
    Stimulation and Simultaneous Pre- and Postsynaptic Recording at Cortical Synapses.”
    <i>Nature Protocols</i>, vol. 16, no. 6, Springer Nature, 2021, pp. 2947–2967,
    doi:<a href="https://doi.org/10.1038/s41596-021-00526-0">10.1038/s41596-021-00526-0</a>.
  short: D.H. Vandael, Y. Okamoto, C. Borges Merjane, V.M. Vargas Barroso, B. Suter,
    P.M. Jonas, Nature Protocols 16 (2021) 2947–2967.
corr_author: '1'
date_created: 2021-05-30T22:01:24Z
date_published: 2021-06-01T00:00:00Z
date_updated: 2025-04-22T22:30:43Z
day: '01'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1038/s41596-021-00526-0
ec_funded: 1
external_id:
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  pmid:
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  grant_number: '692692'
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  name: Synaptic communication in neuronal microcircuits
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publication: Nature Protocols
publication_identifier:
  eissn:
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  issn:
  - 1754-2189
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous
  pre- and postsynaptic recording at cortical synapses
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 16
year: '2021'
...
---
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abstract:
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  text: Pattern separation is a fundamental brain computation that converts small
    differences in input patterns into large differences in output patterns. Several
    synaptic mechanisms of pattern separation have been proposed, including code expansion,
    inhibition and plasticity; however, which of these mechanisms play a role in the
    entorhinal cortex (EC)–dentate gyrus (DG)–CA3 circuit, a classical pattern separation
    circuit, remains unclear. Here we show that a biologically realistic, full-scale
    EC–DG–CA3 circuit model, including granule cells (GCs) and parvalbumin-positive
    inhibitory interneurons (PV+-INs) in the DG, is an efficient pattern separator.
    Both external gamma-modulated inhibition and internal lateral inhibition mediated
    by PV+-INs substantially contributed to pattern separation. Both local connectivity
    and fast signaling at GC–PV+-IN synapses were important for maximum effectiveness.
    Similarly, mossy fiber synapses with conditional detonator properties contributed
    to pattern separation. By contrast, perforant path synapses with Hebbian synaptic
    plasticity and direct EC–CA3 connection shifted the network towards pattern completion.
    Our results demonstrate that the specific properties of cells and synapses optimize
    higher-order computations in biological networks and might be useful to improve
    the deep learning capabilities of technical networks.
acknowledged_ssus:
- _id: SSU
acknowledgement: We thank A. Aertsen, N. Kopell, W. Maass, A. Roth, F. Stella and
  T. Vogels for critically reading earlier versions of the manuscript. We are grateful
  to F. Marr and C. Altmutter for excellent technical assistance, E. Kralli-Beller
  for manuscript editing, and the Scientific Service Units of IST Austria for efficient
  support. Finally, we thank T. Carnevale, L. Erdös, M. Hines, D. Nykamp and D. Schröder
  for useful discussions, and R. Friedrich and S. Wiechert for sharing unpublished
  data. This project received funding from the European Research Council (ERC) under
  the European Union’s Horizon 2020 research and innovation programme (grant agreement
  no. 692692, P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z
  312-B27, Wittgenstein award to P.J. and P 31815 to S.J.G.).
article_processing_charge: No
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author:
- first_name: José
  full_name: Guzmán, José
  id: 30CC5506-F248-11E8-B48F-1D18A9856A87
  last_name: Guzmán
  orcid: 0000-0003-2209-5242
- first_name: Alois
  full_name: Schlögl, Alois
  id: 45BF87EE-F248-11E8-B48F-1D18A9856A87
  last_name: Schlögl
  orcid: 0000-0002-5621-8100
- first_name: 'Claudia '
  full_name: 'Espinoza Martinez, Claudia '
  id: 31FFEE2E-F248-11E8-B48F-1D18A9856A87
  last_name: Espinoza Martinez
  orcid: 0000-0003-4710-2082
- first_name: Xiaomin
  full_name: Zhang, Xiaomin
  id: 423EC9C2-F248-11E8-B48F-1D18A9856A87
  last_name: Zhang
  orcid: 0000-0003-0256-6529
- first_name: Benjamin
  full_name: Suter, Benjamin
  id: 4952F31E-F248-11E8-B48F-1D18A9856A87
  last_name: Suter
  orcid: 0000-0002-9885-6936
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
citation:
  ama: Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. How connectivity
    rules and synaptic properties shape the efficacy of pattern separation in the
    entorhinal cortex–dentate gyrus–CA3 network. <i>Nature Computational Science</i>.
    2021;1(12):830-842. doi:<a href="https://doi.org/10.1038/s43588-021-00157-1">10.1038/s43588-021-00157-1</a>
  apa: Guzmán, J., Schlögl, A., Espinoza Martinez, C., Zhang, X., Suter, B., &#38;
    Jonas, P. M. (2021). How connectivity rules and synaptic properties shape the
    efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network.
    <i>Nature Computational Science</i>. Springer Nature. <a href="https://doi.org/10.1038/s43588-021-00157-1">https://doi.org/10.1038/s43588-021-00157-1</a>
  chicago: Guzmán, José, Alois Schlögl, Claudia  Espinoza Martinez, Xiaomin Zhang,
    Benjamin Suter, and Peter M Jonas. “How Connectivity Rules and Synaptic Properties
    Shape the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3
    Network.” <i>Nature Computational Science</i>. Springer Nature, 2021. <a href="https://doi.org/10.1038/s43588-021-00157-1">https://doi.org/10.1038/s43588-021-00157-1</a>.
  ieee: J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, and P. M.
    Jonas, “How connectivity rules and synaptic properties shape the efficacy of pattern
    separation in the entorhinal cortex–dentate gyrus–CA3 network,” <i>Nature Computational
    Science</i>, vol. 1, no. 12. Springer Nature, pp. 830–842, 2021.
  ista: Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. 2021.
    How connectivity rules and synaptic properties shape the efficacy of pattern separation
    in the entorhinal cortex–dentate gyrus–CA3 network. Nature Computational Science.
    1(12), 830–842.
  mla: Guzmán, José, et al. “How Connectivity Rules and Synaptic Properties Shape
    the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3
    Network.” <i>Nature Computational Science</i>, vol. 1, no. 12, Springer Nature,
    2021, pp. 830–42, doi:<a href="https://doi.org/10.1038/s43588-021-00157-1">10.1038/s43588-021-00157-1</a>.
  short: J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, P.M. Jonas,
    Nature Computational Science 1 (2021) 830–842.
corr_author: '1'
date_created: 2022-03-04T08:32:36Z
date_published: 2021-12-16T00:00:00Z
date_updated: 2025-10-09T22:30:54Z
day: '16'
ddc:
- '610'
department:
- _id: PeJo
doi: 10.1038/s43588-021-00157-1
ec_funded: 1
external_id:
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title: How connectivity rules and synaptic properties shape the efficacy of pattern
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---
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abstract:
- lang: eng
  text: Pattern separation is a fundamental brain computation that converts small
    differences in input patterns into large differences in output patterns. Several
    synaptic mechanisms of pattern separation have been proposed, including code expansion,
    inhibition and plasticity; however, which of these mechanisms play a role in the
    entorhinal cortex (EC)–dentate gyrus (DG)–CA3 circuit, a classical pattern separation
    circuit, remains unclear. Here we show that a biologically realistic, full-scale
    EC–DG–CA3 circuit model, including granule cells (GCs) and parvalbumin-positive
    inhibitory interneurons (PV+-INs) in the DG, is an efficient pattern separator.
    Both external gamma-modulated inhibition and internal lateral inhibition mediated
    by PV+-INs substantially contributed to pattern separation. Both local connectivity
    and fast signaling at GC–PV+-IN synapses were important for maximum effectiveness.
    Similarly, mossy fiber synapses with conditional detonator properties contributed
    to pattern separation. By contrast, perforant path synapses with Hebbian synaptic
    plasticity and direct EC–CA3 connection shifted the network towards pattern completion.
    Our results demonstrate that the specific properties of cells and synapses optimize
    higher-order computations in biological networks and might be useful to improve
    the deep learning capabilities of technical networks.
author:
- first_name: José
  full_name: Guzmán, José
  id: 30CC5506-F248-11E8-B48F-1D18A9856A87
  last_name: Guzmán
  orcid: 0000-0003-2209-5242
- first_name: Alois
  full_name: Schlögl, Alois
  id: 45BF87EE-F248-11E8-B48F-1D18A9856A87
  last_name: Schlögl
  orcid: 0000-0002-5621-8100
- first_name: 'Claudia '
  full_name: 'Espinoza Martinez, Claudia '
  id: 31FFEE2E-F248-11E8-B48F-1D18A9856A87
  last_name: Espinoza Martinez
  orcid: 0000-0003-4710-2082
- first_name: Xiaomin
  full_name: Zhang, Xiaomin
  id: 423EC9C2-F248-11E8-B48F-1D18A9856A87
  last_name: Zhang
  orcid: 0000-0003-0256-6529
- first_name: Benjamin
  full_name: Suter, Benjamin
  id: 4952F31E-F248-11E8-B48F-1D18A9856A87
  last_name: Suter
  orcid: 0000-0002-9885-6936
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
citation:
  ama: Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. How connectivity
    rules and synaptic properties shape the efficacy of pattern separation in the
    entorhinal cortex–dentate gyrus–CA3 network. 2021. doi:<a href="https://doi.org/10.15479/AT:ISTA:10110">10.15479/AT:ISTA:10110</a>
  apa: Guzmán, J., Schlögl, A., Espinoza Martinez, C., Zhang, X., Suter, B., &#38;
    Jonas, P. M. (2021). How connectivity rules and synaptic properties shape the
    efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network.
    IST Austria. <a href="https://doi.org/10.15479/AT:ISTA:10110">https://doi.org/10.15479/AT:ISTA:10110</a>
  chicago: Guzmán, José, Alois Schlögl, Claudia  Espinoza Martinez, Xiaomin Zhang,
    Benjamin Suter, and Peter M Jonas. “How Connectivity Rules and Synaptic Properties
    Shape the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3
    Network.” IST Austria, 2021. <a href="https://doi.org/10.15479/AT:ISTA:10110">https://doi.org/10.15479/AT:ISTA:10110</a>.
  ieee: J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, and P. M.
    Jonas, “How connectivity rules and synaptic properties shape the efficacy of pattern
    separation in the entorhinal cortex–dentate gyrus–CA3 network.” IST Austria, 2021.
  ista: Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. 2021.
    How connectivity rules and synaptic properties shape the efficacy of pattern separation
    in the entorhinal cortex–dentate gyrus–CA3 network, IST Austria, <a href="https://doi.org/10.15479/AT:ISTA:10110">10.15479/AT:ISTA:10110</a>.
  mla: Guzmán, José, et al. <i>How Connectivity Rules and Synaptic Properties Shape
    the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3
    Network</i>. IST Austria, 2021, doi:<a href="https://doi.org/10.15479/AT:ISTA:10110">10.15479/AT:ISTA:10110</a>.
  short: J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, P.M. Jonas,
    (2021).
date_created: 2021-10-08T06:44:22Z
date_published: 2021-12-16T00:00:00Z
date_updated: 2026-06-07T22:30:08Z
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- '005'
department:
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- _id: ScienComp
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title: How connectivity rules and synaptic properties shape the efficacy of pattern
  separation in the entorhinal cortex–dentate gyrus–CA3 network
tmp:
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---
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abstract:
- lang: eng
  text: The synaptic connection from medial habenula (MHb) to interpeduncular nucleus
    (IPN) is critical for emotion-related behaviors and uniquely expresses R-type
    Ca2+ channels (Cav2.3) and auxiliary GABAB receptor (GBR) subunits, the K+-channel
    tetramerization domain-containing proteins (KCTDs). Activation of GBRs facilitates
    or inhibits transmitter release from MHb terminals depending on the IPN subnucleus,
    but the role of KCTDs is unknown. We therefore examined the localization and function
    of Cav2.3, GBRs, and KCTDs in this pathway in mice. We show in heterologous cells
    that KCTD8 and KCTD12b directly bind to Cav2.3 and that KCTD8 potentiates Cav2.3
    currents in the absence of GBRs. In the rostral IPN, KCTD8, KCTD12b, and Cav2.3
    co-localize at the presynaptic active zone. Genetic deletion indicated a bidirectional
    modulation of Cav2.3-mediated release by these KCTDs with a compensatory increase
    of KCTD8 in the active zone in KCTD12b-deficient mice. The interaction of Cav2.3
    with KCTDs therefore scales synaptic strength independent of GBR activation.
acknowledgement: We are grateful to Akari Hagiwara and Toshihisa Ohtsuka for CAST
  antibody, and Masahiko Watanabe for neurexin antibody. We thank David Adams for
  kindly providing the stable Cav2.3 cell line. Cav2.3 KO mice were kindly provided
  by Tsutomu Tanabe. This project has received funding from the European Research
  Council (ERC) and European Commission (EC), under the European Union’s Horizon 2020
  research and innovation programme (ERC grant agreement no. 694539 to Ryuichi Shigemoto,
  no. 692692 to Peter Jonas, and the Marie Skłodowska-Curie grant agreement no. 665385
  to Cihan Önal), the Swiss National Science Foundation Grant 31003A-172881 to Bernhard
  Bettler and Deutsche Forschungsgemeinschaft (For 2143) and BIOSS-2 to Akos Kulik.
article_number: e68274
article_processing_charge: No
article_type: original
author:
- first_name: Pradeep
  full_name: Bhandari, Pradeep
  id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87
  last_name: Bhandari
  orcid: 0000-0003-0863-4481
- first_name: David H
  full_name: Vandael, David H
  id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87
  last_name: Vandael
  orcid: 0000-0001-7577-1676
- first_name: Diego
  full_name: Fernández-Fernández, Diego
  last_name: Fernández-Fernández
- first_name: Thorsten
  full_name: Fritzius, Thorsten
  last_name: Fritzius
- first_name: David
  full_name: Kleindienst, David
  id: 42E121A4-F248-11E8-B48F-1D18A9856A87
  last_name: Kleindienst
- first_name: Hüseyin C
  full_name: Önal, Hüseyin C
  id: 4659D740-F248-11E8-B48F-1D18A9856A87
  last_name: Önal
  orcid: 0000-0002-2771-2011
- first_name: Jacqueline-Claire
  full_name: Montanaro-Punzengruber, Jacqueline-Claire
  id: 3786AB44-F248-11E8-B48F-1D18A9856A87
  last_name: Montanaro-Punzengruber
- first_name: Martin
  full_name: Gassmann, Martin
  last_name: Gassmann
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
- first_name: Akos
  full_name: Kulik, Akos
  last_name: Kulik
- first_name: Bernhard
  full_name: Bettler, Bernhard
  last_name: Bettler
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
- first_name: Peter
  full_name: Koppensteiner, Peter
  id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
  last_name: Koppensteiner
  orcid: 0000-0002-3509-1948
citation:
  ama: Bhandari P, Vandael DH, Fernández-Fernández D, et al. GABAB receptor auxiliary
    subunits modulate Cav2.3-mediated release from medial habenula terminals. <i>eLife</i>.
    2021;10. doi:<a href="https://doi.org/10.7554/ELIFE.68274">10.7554/ELIFE.68274</a>
  apa: Bhandari, P., Vandael, D. H., Fernández-Fernández, D., Fritzius, T., Kleindienst,
    D., Önal, C., … Koppensteiner, P. (2021). GABAB receptor auxiliary subunits modulate
    Cav2.3-mediated release from medial habenula terminals. <i>ELife</i>. eLife Sciences
    Publications. <a href="https://doi.org/10.7554/ELIFE.68274">https://doi.org/10.7554/ELIFE.68274</a>
  chicago: Bhandari, Pradeep, David H Vandael, Diego Fernández-Fernández, Thorsten
    Fritzius, David Kleindienst, Cihan Önal, Jacqueline-Claire Montanaro-Punzengruber,
    et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from
    Medial Habenula Terminals.” <i>ELife</i>. eLife Sciences Publications, 2021. <a
    href="https://doi.org/10.7554/ELIFE.68274">https://doi.org/10.7554/ELIFE.68274</a>.
  ieee: P. Bhandari <i>et al.</i>, “GABAB receptor auxiliary subunits modulate Cav2.3-mediated
    release from medial habenula terminals,” <i>eLife</i>, vol. 10. eLife Sciences
    Publications, 2021.
  ista: Bhandari P, Vandael DH, Fernández-Fernández D, Fritzius T, Kleindienst D,
    Önal C, Montanaro-Punzengruber J-C, Gassmann M, Jonas PM, Kulik A, Bettler B,
    Shigemoto R, Koppensteiner P. 2021. GABAB receptor auxiliary subunits modulate
    Cav2.3-mediated release from medial habenula terminals. eLife. 10, e68274.
  mla: Bhandari, Pradeep, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated
    Release from Medial Habenula Terminals.” <i>ELife</i>, vol. 10, e68274, eLife
    Sciences Publications, 2021, doi:<a href="https://doi.org/10.7554/ELIFE.68274">10.7554/ELIFE.68274</a>.
  short: P. Bhandari, D.H. Vandael, D. Fernández-Fernández, T. Fritzius, D. Kleindienst,
    C. Önal, J.-C. Montanaro-Punzengruber, M. Gassmann, P.M. Jonas, A. Kulik, B. Bettler,
    R. Shigemoto, P. Koppensteiner, ELife 10 (2021).
date_created: 2021-05-30T22:01:23Z
date_published: 2021-04-29T00:00:00Z
date_updated: 2026-06-07T22:30:43Z
day: '29'
ddc:
- '570'
department:
- _id: RySh
- _id: PeJo
doi: 10.7554/ELIFE.68274
ec_funded: 1
external_id:
  isi:
  - '000651761700001'
  pmid:
  - '33913808'
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oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25CA28EA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '694539'
  name: 'In situ analysis of single channel subunit composition in neurons: physiological
    implication in synaptic plasticity and behaviour'
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
  link:
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  record:
  - id: '19271'
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    status: public
  - id: '9562'
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    status: public
scopus_import: '1'
status: public
title: GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial
  habenula terminals
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 10
year: '2021'
...
---
_id: '8001'
abstract:
- lang: eng
  text: Post-tetanic potentiation (PTP) is an attractive candidate mechanism for hippocampus-dependent
    short-term memory. Although PTP has a uniquely large magnitude at hippocampal
    mossy fiber-CA3 pyramidal neuron synapses, it is unclear whether it can be induced
    by natural activity and whether its lifetime is sufficient to support short-term
    memory. We combined in vivo recordings from granule cells (GCs), in vitro paired
    recordings from mossy fiber terminals and postsynaptic CA3 neurons, and “flash
    and freeze” electron microscopy. PTP was induced at single synapses and showed
    a low induction threshold adapted to sparse GC activity in vivo. PTP was mainly
    generated by enlargement of the readily releasable pool of synaptic vesicles,
    allowing multiplicative interaction with other plasticity forms. PTP was associated
    with an increase in the docked vesicle pool, suggesting formation of structural
    “pool engrams.” Absence of presynaptic activity extended the lifetime of the potentiation,
    enabling prolonged information storage in the hippocampal network.
acknowledged_ssus:
- _id: SSU
acknowledgement: This project received funding from the European Research Council
  (ERC) under the European Union Horizon 2020 Research and Innovation Program (grant
  agreement 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung
  ( Z 312-B27 , Wittgenstein award to P.J. and V 739-B27 to C.B.-M.). We thank Drs.
  Jozsef Csicsvari, Jose Guzman, Erwin Neher, and Ryuichi Shigemoto for commenting
  on earlier versions of the manuscript. We are grateful to Walter Kaufmann, Daniel
  Gütl, and Vanessa Zheden for EM training; Alois Schlögl for programming; Florian
  Marr for excellent technical assistance and cell reconstruction; Christina Altmutter
  for technical help; Eleftheria Kralli-Beller for manuscript editing; Taija Makinen
  for providing the Prox1-CreERT2 mouse line; and the Scientific Service Units of
  IST Austria for support.
article_processing_charge: No
article_type: original
author:
- first_name: David H
  full_name: Vandael, David H
  id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87
  last_name: Vandael
  orcid: 0000-0001-7577-1676
- first_name: Carolina
  full_name: Borges Merjane, Carolina
  id: 4305C450-F248-11E8-B48F-1D18A9856A87
  last_name: Borges Merjane
  orcid: 0000-0003-0005-401X
- first_name: Xiaomin
  full_name: Zhang, Xiaomin
  id: 423EC9C2-F248-11E8-B48F-1D18A9856A87
  last_name: Zhang
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
citation:
  ama: Vandael DH, Borges Merjane C, Zhang X, Jonas PM. Short-term plasticity at hippocampal
    mossy fiber synapses is induced by natural activity patterns and associated with
    vesicle pool engram formation. <i>Neuron</i>. 2020;107(3):509-521. doi:<a href="https://doi.org/10.1016/j.neuron.2020.05.013">10.1016/j.neuron.2020.05.013</a>
  apa: Vandael, D. H., Borges Merjane, C., Zhang, X., &#38; Jonas, P. M. (2020). Short-term
    plasticity at hippocampal mossy fiber synapses is induced by natural activity
    patterns and associated with vesicle pool engram formation. <i>Neuron</i>. Elsevier.
    <a href="https://doi.org/10.1016/j.neuron.2020.05.013">https://doi.org/10.1016/j.neuron.2020.05.013</a>
  chicago: Vandael, David H, Carolina Borges Merjane, Xiaomin Zhang, and Peter M Jonas.
    “Short-Term Plasticity at Hippocampal Mossy Fiber Synapses Is Induced by Natural
    Activity Patterns and Associated with Vesicle Pool Engram Formation.” <i>Neuron</i>.
    Elsevier, 2020. <a href="https://doi.org/10.1016/j.neuron.2020.05.013">https://doi.org/10.1016/j.neuron.2020.05.013</a>.
  ieee: D. H. Vandael, C. Borges Merjane, X. Zhang, and P. M. Jonas, “Short-term plasticity
    at hippocampal mossy fiber synapses is induced by natural activity patterns and
    associated with vesicle pool engram formation,” <i>Neuron</i>, vol. 107, no. 3.
    Elsevier, pp. 509–521, 2020.
  ista: Vandael DH, Borges Merjane C, Zhang X, Jonas PM. 2020. Short-term plasticity
    at hippocampal mossy fiber synapses is induced by natural activity patterns and
    associated with vesicle pool engram formation. Neuron. 107(3), 509–521.
  mla: Vandael, David H., et al. “Short-Term Plasticity at Hippocampal Mossy Fiber
    Synapses Is Induced by Natural Activity Patterns and Associated with Vesicle Pool
    Engram Formation.” <i>Neuron</i>, vol. 107, no. 3, Elsevier, 2020, pp. 509–21,
    doi:<a href="https://doi.org/10.1016/j.neuron.2020.05.013">10.1016/j.neuron.2020.05.013</a>.
  short: D.H. Vandael, C. Borges Merjane, X. Zhang, P.M. Jonas, Neuron 107 (2020)
    509–521.
corr_author: '1'
date_created: 2020-06-22T13:29:05Z
date_published: 2020-08-05T00:00:00Z
date_updated: 2025-04-15T08:29:09Z
day: '05'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1016/j.neuron.2020.05.013
ec_funded: 1
external_id:
  isi:
  - '000556135600004'
  pmid:
  - '32492366'
file:
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  creator: dernst
  date_created: 2020-11-25T11:23:02Z
  date_updated: 2020-11-25T11:23:02Z
  file_id: '8811'
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  success: 1
file_date_updated: 2020-11-25T11:23:02Z
has_accepted_license: '1'
intvolume: '       107'
isi: 1
issue: '3'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: 509-521
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z00312
  name: Synaptic communication in neuronal microcircuits
- _id: 2696E7FE-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: V00739
  name: Structural plasticity at mossy fiber-CA3 synapses
publication: Neuron
publication_identifier:
  eissn:
  - '10974199'
  issn:
  - 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/possible-physical-trace-of-short-term-memory-found/
scopus_import: '1'
status: public
title: Short-term plasticity at hippocampal mossy fiber synapses is induced by natural
  activity patterns and associated with vesicle pool engram formation
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
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  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 107
year: '2020'
...
---
_id: '8261'
abstract:
- lang: eng
  text: Dentate gyrus granule cells (GCs) connect the entorhinal cortex to the hippocampal
    CA3 region, but how they process spatial information remains enigmatic. To examine
    the role of GCs in spatial coding, we measured excitatory postsynaptic potentials
    (EPSPs) and action potentials (APs) in head-fixed mice running on a linear belt.
    Intracellular recording from morphologically identified GCs revealed that most
    cells were active, but activity level varied over a wide range. Whereas only ∼5%
    of GCs showed spatially tuned spiking, ∼50% received spatially tuned input. Thus,
    the GC population broadly encodes spatial information, but only a subset relays
    this information to the CA3 network. Fourier analysis indicated that GCs received
    conjunctive place-grid-like synaptic input, suggesting code conversion in single
    neurons. GC firing was correlated with dendritic complexity and intrinsic excitability,
    but not extrinsic excitatory input or dendritic cable properties. Thus, functional
    maturation may control input-output transformation and spatial code conversion.
acknowledged_ssus:
- _id: M-Shop
- _id: ScienComp
- _id: PreCl
acknowledgement: This project has received funding from the European Research Council
  (ERC) under the European Union’s Horizon 2020 research and innovation program (grant
  agreement 692692, P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung
  (Z 312-B27, Wittgenstein award, P.J.). We thank Gyorgy Buzsáki, Jozsef Csicsvari,
  Juan Ramirez Villegas, and Federico Stella for commenting on earlier versions of
  this manuscript. We also thank Katie Bittner, Michael Brecht, Albert Lee, Jeffery
  Magee, and Alejandro Pernía-Andrade for sharing expertise in in vivo patch-clamp
  recording. We are grateful to Florian Marr for cell labeling, cell reconstruction,
  and technical assistance; Ben Suter for helpful discussions; Christina Altmutter
  for technical support; Eleftheria Kralli-Beller for manuscript editing; and Todor
  Asenov (Machine Shop) for device construction. We also thank the Scientific Service
  Units (SSUs) of IST Austria (Machine Shop, Scientific Computing, and Preclinical
  Facility) for efficient support.
article_processing_charge: No
article_type: original
author:
- first_name: Xiaomin
  full_name: Zhang, Xiaomin
  id: 423EC9C2-F248-11E8-B48F-1D18A9856A87
  last_name: Zhang
- first_name: Alois
  full_name: Schlögl, Alois
  id: 45BF87EE-F248-11E8-B48F-1D18A9856A87
  last_name: Schlögl
  orcid: 0000-0002-5621-8100
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
citation:
  ama: Zhang X, Schlögl A, Jonas PM. Selective routing of spatial information flow
    from input to output in hippocampal granule cells. <i>Neuron</i>. 2020;107(6):1212-1225.
    doi:<a href="https://doi.org/10.1016/j.neuron.2020.07.006">10.1016/j.neuron.2020.07.006</a>
  apa: Zhang, X., Schlögl, A., &#38; Jonas, P. M. (2020). Selective routing of spatial
    information flow from input to output in hippocampal granule cells. <i>Neuron</i>.
    Elsevier. <a href="https://doi.org/10.1016/j.neuron.2020.07.006">https://doi.org/10.1016/j.neuron.2020.07.006</a>
  chicago: Zhang, Xiaomin, Alois Schlögl, and Peter M Jonas. “Selective Routing of
    Spatial Information Flow from Input to Output in Hippocampal Granule Cells.” <i>Neuron</i>.
    Elsevier, 2020. <a href="https://doi.org/10.1016/j.neuron.2020.07.006">https://doi.org/10.1016/j.neuron.2020.07.006</a>.
  ieee: X. Zhang, A. Schlögl, and P. M. Jonas, “Selective routing of spatial information
    flow from input to output in hippocampal granule cells,” <i>Neuron</i>, vol. 107,
    no. 6. Elsevier, pp. 1212–1225, 2020.
  ista: Zhang X, Schlögl A, Jonas PM. 2020. Selective routing of spatial information
    flow from input to output in hippocampal granule cells. Neuron. 107(6), 1212–1225.
  mla: Zhang, Xiaomin, et al. “Selective Routing of Spatial Information Flow from
    Input to Output in Hippocampal Granule Cells.” <i>Neuron</i>, vol. 107, no. 6,
    Elsevier, 2020, pp. 1212–25, doi:<a href="https://doi.org/10.1016/j.neuron.2020.07.006">10.1016/j.neuron.2020.07.006</a>.
  short: X. Zhang, A. Schlögl, P.M. Jonas, Neuron 107 (2020) 1212–1225.
corr_author: '1'
date_created: 2020-08-14T09:36:05Z
date_published: 2020-09-23T00:00:00Z
date_updated: 2025-04-15T08:29:03Z
day: '23'
ddc:
- '570'
department:
- _id: PeJo
- _id: ScienComp
doi: 10.1016/j.neuron.2020.07.006
ec_funded: 1
external_id:
  isi:
  - '000579698700009'
  pmid:
  - '32763145'
file:
- access_level: open_access
  checksum: 44a5960fc083a4cb3488d22224859fdc
  content_type: application/pdf
  creator: dernst
  date_created: 2020-12-04T09:29:21Z
  date_updated: 2020-12-04T09:29:21Z
  file_id: '8920'
  file_name: 2020_Neuron_Zhang.pdf
  file_size: 3011120
  relation: main_file
  success: 1
file_date_updated: 2020-12-04T09:29:21Z
has_accepted_license: '1'
intvolume: '       107'
isi: 1
issue: '6'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: 1212-1225
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z00312
  name: Synaptic communication in neuronal microcircuits
publication: Neuron
publication_identifier:
  issn:
  - 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Website
    relation: press_release
    url: https://ist.ac.at/en/news/the-bouncer-in-the-brain/
scopus_import: '1'
status: public
title: Selective routing of spatial information flow from input to output in hippocampal
  granule cells
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 107
year: '2020'
...
---
_id: '7473'
abstract:
- lang: eng
  text: How structural and functional properties of synapses relate to each other
    is a fundamental question in neuroscience. Electrophysiology has elucidated mechanisms
    of synaptic transmission, and electron microscopy (EM) has provided insight into
    morphological properties of synapses. Here we describe an enhanced method for
    functional EM (“flash and freeze”), combining optogenetic stimulation with high-pressure
    freezing. We demonstrate that the improved method can be applied to intact networks
    in acute brain slices and organotypic slice cultures from mice. As a proof of
    concept, we probed vesicle pool changes during synaptic transmission at the hippocampal
    mossy fiber-CA3 pyramidal neuron synapse. Our findings show overlap of the docked
    vesicle pool and the functionally defined readily releasable pool and provide
    evidence of fast endocytosis at this synapse. Functional EM with acute slices
    and slice cultures has the potential to reveal the structural and functional mechanisms
    of transmission in intact, genetically perturbed, and disease-affected synapses.
acknowledgement: This project has received funding from the European Research Council
  (ERC) and European Commission (EC), under the European Union’s Horizon 2020 research
  and innovation programme (ERC grant agreement No. 692692 and Marie Sklodowska-Curie
  708497) and from Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27
  Wittgenstein award and DK W1205-B09). We thank Johann Danzl and Ryuichi Shigemoto
  for critically reading the manuscript; Walter Kaufmann, Daniel Gutl, and Vanessa
  Zheden for extensive EM training, advice, and experimental assistance; Benjamin
  Suter for substantial help with light stimulation, ImageJ plugins for analysis,
  and manuscript editing; Florian Marr and Christina Altmutter for technical support;
  Eleftheria Kralli-Beller for manuscript editing; Julia König and Paul Wurzinger
  (Leica Microsystems) for helpful technical discussions; and Taija Makinen for providing
  the Prox1-CreERT2 mouse line.
article_processing_charge: No
article_type: original
author:
- first_name: Carolina
  full_name: Borges Merjane, Carolina
  id: 4305C450-F248-11E8-B48F-1D18A9856A87
  last_name: Borges Merjane
  orcid: 0000-0003-0005-401X
- first_name: Olena
  full_name: Kim, Olena
  id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87
  last_name: Kim
  orcid: 0000-0003-2344-1039
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
citation:
  ama: Borges Merjane C, Kim O, Jonas PM. Functional electron microscopy (“Flash and
    Freeze”) of identified cortical synapses in acute brain slices. <i>Neuron</i>.
    2020;105:992-1006. doi:<a href="https://doi.org/10.1016/j.neuron.2019.12.022">10.1016/j.neuron.2019.12.022</a>
  apa: Borges Merjane, C., Kim, O., &#38; Jonas, P. M. (2020). Functional electron
    microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain
    slices. <i>Neuron</i>. Elsevier. <a href="https://doi.org/10.1016/j.neuron.2019.12.022">https://doi.org/10.1016/j.neuron.2019.12.022</a>
  chicago: Borges Merjane, Carolina, Olena Kim, and Peter M Jonas. “Functional Electron
    Microscopy (‘Flash and Freeze’) of Identified Cortical Synapses in Acute Brain
    Slices.” <i>Neuron</i>. Elsevier, 2020. <a href="https://doi.org/10.1016/j.neuron.2019.12.022">https://doi.org/10.1016/j.neuron.2019.12.022</a>.
  ieee: C. Borges Merjane, O. Kim, and P. M. Jonas, “Functional electron microscopy
    (‘Flash and Freeze’) of identified cortical synapses in acute brain slices,” <i>Neuron</i>,
    vol. 105. Elsevier, pp. 992–1006, 2020.
  ista: Borges Merjane C, Kim O, Jonas PM. 2020. Functional electron microscopy (“Flash
    and Freeze”) of identified cortical synapses in acute brain slices. Neuron. 105,
    992–1006.
  mla: Borges Merjane, Carolina, et al. “Functional Electron Microscopy (‘Flash and
    Freeze’) of Identified Cortical Synapses in Acute Brain Slices.” <i>Neuron</i>,
    vol. 105, Elsevier, 2020, pp. 992–1006, doi:<a href="https://doi.org/10.1016/j.neuron.2019.12.022">10.1016/j.neuron.2019.12.022</a>.
  short: C. Borges Merjane, O. Kim, P.M. Jonas, Neuron 105 (2020) 992–1006.
corr_author: '1'
date_created: 2020-02-10T15:59:45Z
date_published: 2020-03-18T00:00:00Z
date_updated: 2026-06-07T22:30:30Z
day: '18'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1016/j.neuron.2019.12.022
ec_funded: 1
external_id:
  isi:
  - '000520854700008'
  pmid:
  - '31928842'
file:
- access_level: open_access
  checksum: 3582664addf26859e86ac5bec3e01416
  content_type: application/pdf
  creator: dernst
  date_created: 2020-11-20T08:58:53Z
  date_updated: 2020-11-20T08:58:53Z
  file_id: '8778'
  file_name: 2020_Neuron_BorgesMerjane.pdf
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file_date_updated: 2020-11-20T08:58:53Z
has_accepted_license: '1'
intvolume: '       105'
isi: 1
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: 992-1006
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 25BAF7B2-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '708497'
  name: Presynaptic calcium channels distribution and impact on coupling at the hippocampal
    mossy fiber synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z00312
  name: Synaptic communication in neuronal microcircuits
- _id: 25C3DBB6-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W01205
  name: Zellkommunikation in Gesundheit und Krankheit
publication: Neuron
publication_identifier:
  issn:
  - 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/flash-and-freeze-reveals-dynamics-of-nerve-connections/
  record:
  - id: '11196'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Functional electron microscopy (“Flash and Freeze”) of identified cortical
  synapses in acute brain slices
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 105
year: '2020'
...
---
OA_type: closed access
_id: '19989'
abstract:
- lang: ger
  text: Neurone empfangen Eingangssignale, konvertieren diese in Aktionspotenziale
    und generieren schließlich Ausgangssignale auf ihren Zielzellen. Dabei sind die
    zu überwindenden räumlichen Distanzen oft groß. Daher ist entscheidend, dass elektrische
    Signale in Nervenzellen schnell von einem zum anderen Ort geleitet werden können.
    Diese wichtige Aufgabe erfüllt das Axon, der „Ausgangsfortsatz“ der Nervenzelle.
    Für die schnelle Leitung des Aktionspotenzials sind sowohl die passiven Eigenschaften
    des axonalen Kabels als auch die aktiven Eigenschaften der Zellmembran von entscheidender
    Bedeutung. Die Evolution bedient sich zweier Tricks, um die Leitungsgeschwindigkeit
    des Aktionspotenzials zu maximieren. Der eine Trick ist die Zunahme des Axondurchmessers.
    Der andere Trick ist die Ausbildung von Markscheiden. Dies führt bei nahezu gleichem
    Platzbedarf zu einer Zunahme der Leistungsgeschwindigkeit um fast zwei Größenordnungen.
    Die Aktionspotenzialleitung an myelinisierten Axonen erfolgt „saltatorisch“.
article_processing_charge: No
author:
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
citation:
  ama: 'Jonas PM. Aktionspotenzial: Fortleitung im Axon. In: <i>Physiologie des Menschen</i>.
    32nd ed. Springer-Lehrbuch. Berlin, Heidelberg: Springer Nature; 2019:72-82. doi:<a
    href="https://doi.org/10.1007/978-3-662-56468-4_7">10.1007/978-3-662-56468-4_7</a>'
  apa: 'Jonas, P. M. (2019). Aktionspotenzial: Fortleitung im Axon. In <i>Physiologie
    des Menschen</i> (32nd ed., pp. 72–82). Berlin, Heidelberg: Springer Nature. <a
    href="https://doi.org/10.1007/978-3-662-56468-4_7">https://doi.org/10.1007/978-3-662-56468-4_7</a>'
  chicago: 'Jonas, Peter M. “Aktionspotenzial: Fortleitung im Axon.” In <i>Physiologie
    des Menschen</i>, 32nd ed., 72–82. Springer-Lehrbuch. Berlin, Heidelberg: Springer
    Nature, 2019. <a href="https://doi.org/10.1007/978-3-662-56468-4_7">https://doi.org/10.1007/978-3-662-56468-4_7</a>.'
  ieee: 'P. M. Jonas, “Aktionspotenzial: Fortleitung im Axon,” in <i>Physiologie des
    Menschen</i>, 32nd ed., Berlin, Heidelberg: Springer Nature, 2019, pp. 72–82.'
  ista: 'Jonas PM. 2019.Aktionspotenzial: Fortleitung im Axon. In: Physiologie des
    Menschen. , 72–82.'
  mla: 'Jonas, Peter M. “Aktionspotenzial: Fortleitung im Axon.” <i>Physiologie des
    Menschen</i>, 32nd ed., Springer Nature, 2019, pp. 72–82, doi:<a href="https://doi.org/10.1007/978-3-662-56468-4_7">10.1007/978-3-662-56468-4_7</a>.'
  short: P.M. Jonas, in:, Physiologie des Menschen, 32nd ed., Springer Nature, Berlin,
    Heidelberg, 2019, pp. 72–82.
corr_author: '1'
date_created: 2025-07-10T13:36:36Z
date_published: 2019-04-02T00:00:00Z
date_updated: 2025-09-23T11:44:57Z
day: '02'
department:
- _id: PeJo
doi: 10.1007/978-3-662-56468-4_7
edition: '32'
language:
- iso: ger
month: '04'
oa_version: None
page: 72-82
place: Berlin, Heidelberg
publication: Physiologie des Menschen
publication_identifier:
  eisbn:
  - '9783662564684'
  eissn:
  - 2512-5214
  isbn:
  - '9783662564677'
  issn:
  - 0937-7433
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
series_title: Springer-Lehrbuch
status: public
title: 'Aktionspotenzial: Fortleitung im Axon'
type: book_chapter
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2019'
...
---
_id: '7405'
abstract:
- lang: eng
  text: Biophysical modeling of neuronal networks helps to integrate and interpret
    rapidly growing and disparate experimental datasets at multiple scales. The NetPyNE
    tool (www.netpyne.org) provides both programmatic and graphical interfaces to
    develop data-driven multiscale network models in NEURON. NetPyNE clearly separates
    model parameters from implementation code. Users provide specifications at a high
    level via a standardized declarative language, for example connectivity rules,
    to create millions of cell-to-cell connections. NetPyNE then enables users to
    generate the NEURON network, run efficiently parallelized simulations, optimize
    and explore network parameters through automated batch runs, and use built-in
    functions for visualization and analysis – connectivity matrices, voltage traces,
    spike raster plots, local field potentials, and information theoretic measures.
    NetPyNE also facilitates model sharing by exporting and importing standardized
    formats (NeuroML and SONATA). NetPyNE is already being used to teach computational
    neuroscience students and by modelers to investigate brain regions and phenomena.
article_number: e44494
article_processing_charge: No
article_type: original
author:
- first_name: Salvador
  full_name: Dura-Bernal, Salvador
  last_name: Dura-Bernal
- first_name: Benjamin
  full_name: Suter, Benjamin
  id: 4952F31E-F248-11E8-B48F-1D18A9856A87
  last_name: Suter
  orcid: 0000-0002-9885-6936
- first_name: Padraig
  full_name: Gleeson, Padraig
  last_name: Gleeson
- first_name: Matteo
  full_name: Cantarelli, Matteo
  last_name: Cantarelli
- first_name: Adrian
  full_name: Quintana, Adrian
  last_name: Quintana
- first_name: Facundo
  full_name: Rodriguez, Facundo
  last_name: Rodriguez
- first_name: David J
  full_name: Kedziora, David J
  last_name: Kedziora
- first_name: George L
  full_name: Chadderdon, George L
  last_name: Chadderdon
- first_name: Cliff C
  full_name: Kerr, Cliff C
  last_name: Kerr
- first_name: Samuel A
  full_name: Neymotin, Samuel A
  last_name: Neymotin
- first_name: Robert A
  full_name: McDougal, Robert A
  last_name: McDougal
- first_name: Michael
  full_name: Hines, Michael
  last_name: Hines
- first_name: Gordon MG
  full_name: Shepherd, Gordon MG
  last_name: Shepherd
- first_name: William W
  full_name: Lytton, William W
  last_name: Lytton
citation:
  ama: Dura-Bernal S, Suter B, Gleeson P, et al. NetPyNE, a tool for data-driven multiscale
    modeling of brain circuits. <i>eLife</i>. 2019;8. doi:<a href="https://doi.org/10.7554/elife.44494">10.7554/elife.44494</a>
  apa: Dura-Bernal, S., Suter, B., Gleeson, P., Cantarelli, M., Quintana, A., Rodriguez,
    F., … Lytton, W. W. (2019). NetPyNE, a tool for data-driven multiscale modeling
    of brain circuits. <i>ELife</i>. eLife Sciences Publications. <a href="https://doi.org/10.7554/elife.44494">https://doi.org/10.7554/elife.44494</a>
  chicago: Dura-Bernal, Salvador, Benjamin Suter, Padraig Gleeson, Matteo Cantarelli,
    Adrian Quintana, Facundo Rodriguez, David J Kedziora, et al. “NetPyNE, a Tool
    for Data-Driven Multiscale Modeling of Brain Circuits.” <i>ELife</i>. eLife Sciences
    Publications, 2019. <a href="https://doi.org/10.7554/elife.44494">https://doi.org/10.7554/elife.44494</a>.
  ieee: S. Dura-Bernal <i>et al.</i>, “NetPyNE, a tool for data-driven multiscale
    modeling of brain circuits,” <i>eLife</i>, vol. 8. eLife Sciences Publications,
    2019.
  ista: Dura-Bernal S, Suter B, Gleeson P, Cantarelli M, Quintana A, Rodriguez F,
    Kedziora DJ, Chadderdon GL, Kerr CC, Neymotin SA, McDougal RA, Hines M, Shepherd
    GM, Lytton WW. 2019. NetPyNE, a tool for data-driven multiscale modeling of brain
    circuits. eLife. 8, e44494.
  mla: Dura-Bernal, Salvador, et al. “NetPyNE, a Tool for Data-Driven Multiscale Modeling
    of Brain Circuits.” <i>ELife</i>, vol. 8, e44494, eLife Sciences Publications,
    2019, doi:<a href="https://doi.org/10.7554/elife.44494">10.7554/elife.44494</a>.
  short: S. Dura-Bernal, B. Suter, P. Gleeson, M. Cantarelli, A. Quintana, F. Rodriguez,
    D.J. Kedziora, G.L. Chadderdon, C.C. Kerr, S.A. Neymotin, R.A. McDougal, M. Hines,
    G.M. Shepherd, W.W. Lytton, ELife 8 (2019).
date_created: 2020-01-30T09:08:01Z
date_published: 2019-05-31T00:00:00Z
date_updated: 2023-09-07T14:27:52Z
day: '31'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.7554/elife.44494
external_id:
  isi:
  - '000468968400001'
  pmid:
  - '31025934'
file:
- access_level: open_access
  checksum: 7014189c11c10a12feeeae37f054871d
  content_type: application/pdf
  creator: dernst
  date_created: 2020-02-04T08:41:47Z
  date_updated: 2020-07-14T12:47:57Z
  file_id: '7444'
  file_name: 2019_eLife_DuraBernal.pdf
  file_size: 6182359
  relation: main_file
file_date_updated: 2020-07-14T12:47:57Z
has_accepted_license: '1'
intvolume: '         8'
isi: 1
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
pmid: 1
publication: eLife
publication_identifier:
  issn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: NetPyNE, a tool for data-driven multiscale modeling of brain circuits
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 8
year: '2019'
...
---
_id: '11222'
acknowledgement: This work was supported by the ERC and EU Horizon 2020 (ERC 692692;
  MSC-IF 708497) and FWF Z 312-B27 Wittgenstein award; W 1205-B09).
article_number: A3.27
article_processing_charge: No
author:
- first_name: Olena
  full_name: Kim, Olena
  id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87
  last_name: Kim
  orcid: 0000-0003-2344-1039
- first_name: Carolina
  full_name: Borges Merjane, Carolina
  id: 4305C450-F248-11E8-B48F-1D18A9856A87
  last_name: Borges Merjane
  orcid: 0000-0003-0005-401X
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
citation:
  ama: 'Kim O, Borges Merjane C, Jonas PM. Functional analysis of the docked vesicle
    pool in hippocampal mossy fiber terminals by electron microscopy. In: <i>Intrinsic
    Activity</i>. Vol 7. Austrian Pharmacological Society; 2019. doi:<a href="https://doi.org/10.25006/ia.7.s1-a3.27">10.25006/ia.7.s1-a3.27</a>'
  apa: 'Kim, O., Borges Merjane, C., &#38; Jonas, P. M. (2019). Functional analysis
    of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy.
    In <i>Intrinsic Activity</i> (Vol. 7). Innsbruck, Austria: Austrian Pharmacological
    Society. <a href="https://doi.org/10.25006/ia.7.s1-a3.27">https://doi.org/10.25006/ia.7.s1-a3.27</a>'
  chicago: Kim, Olena, Carolina Borges Merjane, and Peter M Jonas. “Functional Analysis
    of the Docked Vesicle Pool in Hippocampal Mossy Fiber Terminals by Electron Microscopy.”
    In <i>Intrinsic Activity</i>, Vol. 7. Austrian Pharmacological Society, 2019.
    <a href="https://doi.org/10.25006/ia.7.s1-a3.27">https://doi.org/10.25006/ia.7.s1-a3.27</a>.
  ieee: O. Kim, C. Borges Merjane, and P. M. Jonas, “Functional analysis of the docked
    vesicle pool in hippocampal mossy fiber terminals by electron microscopy,” in
    <i>Intrinsic Activity</i>, Innsbruck, Austria, 2019, vol. 7, no. Suppl. 1.
  ista: 'Kim O, Borges Merjane C, Jonas PM. 2019. Functional analysis of the docked
    vesicle pool in hippocampal mossy fiber terminals by electron microscopy. Intrinsic
    Activity. ANA: Austrian Neuroscience Association ; APHAR: Austrian Pharmacological
    Society vol. 7, A3.27.'
  mla: Kim, Olena, et al. “Functional Analysis of the Docked Vesicle Pool in Hippocampal
    Mossy Fiber Terminals by Electron Microscopy.” <i>Intrinsic Activity</i>, vol.
    7, no. Suppl. 1, A3.27, Austrian Pharmacological Society, 2019, doi:<a href="https://doi.org/10.25006/ia.7.s1-a3.27">10.25006/ia.7.s1-a3.27</a>.
  short: O. Kim, C. Borges Merjane, P.M. Jonas, in:, Intrinsic Activity, Austrian
    Pharmacological Society, 2019.
conference:
  end_date: 2019-09-27
  location: Innsbruck, Austria
  name: 'ANA: Austrian Neuroscience Association ; APHAR: Austrian Pharmacological
    Society'
  start_date: 2019-09-25
corr_author: '1'
date_created: 2022-04-20T15:06:05Z
date_published: 2019-09-11T00:00:00Z
date_updated: 2026-06-07T22:30:30Z
day: '11'
department:
- _id: PeJo
doi: 10.25006/ia.7.s1-a3.27
ec_funded: 1
intvolume: '         7'
issue: Suppl. 1
keyword:
- hippocampus
- mossy fibers
- readily releasable pool
- electron microscopy
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.intrinsicactivity.org/2019/7/S1/A3.27/
month: '09'
oa: 1
oa_version: Published Version
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 25BAF7B2-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '708497'
  name: Presynaptic calcium channels distribution and impact on coupling at the hippocampal
    mossy fiber synapse
- _id: 25C3DBB6-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W01205
  name: Zellkommunikation in Gesundheit und Krankheit
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z00312
  name: Synaptic communication in neuronal microcircuits
publication: Intrinsic Activity
publication_identifier:
  issn:
  - 2309-8503
publication_status: published
publisher: Austrian Pharmacological Society
quality_controlled: '1'
related_material:
  record:
  - id: '11196'
    relation: dissertation_contains
    status: public
status: public
title: Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals
  by electron microscopy
type: conference_abstract
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
volume: 7
year: '2019'
...
