---
_id: '15117'
abstract:
- lang: eng
  text: 'The hippocampal mossy fiber synapse, formed between axons of dentate gyrus
    granule cells and dendrites of CA3 pyramidal neurons, is a key synapse in the
    trisynaptic circuitry of the hippocampus. Because of its comparatively large size,
    this synapse is accessible to direct presynaptic recording, allowing a rigorous
    investigation of the biophysical mechanisms of synaptic transmission and plasticity.
    Furthermore, because of its placement in the very center of the hippocampal memory
    circuit, this synapse seems to be critically involved in several higher network
    functions, such as learning, memory, pattern separation, and pattern completion.
    Recent work based on new technologies in both nanoanatomy and nanophysiology,
    including presynaptic patch-clamp recording, paired recording, super-resolution
    light microscopy, and freeze-fracture and “flash-and-freeze” electron microscopy,
    has provided new insights into the structure, biophysics, and network function
    of this intriguing synapse. This brings us one step closer to answering a fundamental
    question in neuroscience: how basic synaptic properties shape higher network computations.'
acknowledgement: "We thank previous students, postdocs, and collaborators, particularly
  J. Geiger, and (in alphabetical order) H. Alle, J. Bischofberger, C. Borges-Merjane,
  D. Engel, M. Frotscher, S. Hallermann, M. Heckmann, S. Jamrichova, O. Kim, L. Li,
  K. Lichter, P. Lin, J. Lübke, Y. Okamoto, C. Pawlu, C. Schmidt-Hieber, N. Spruston,
  and N. Vyleta for their outstanding experimental contributions. We also thank P.
  Castillo, J. Geiger, T. Sakaba, S. Siegert, T. Vogels, and J. Watson for critically
  reading the manuscript, E. Kralli-Beller for text editing, and J. Malikovic and
  L. Slomianka for useful discussions. We apologize that, due to space constraints,
  not all relevant papers could be cited.\r\nThis project was supported by the European
  Research Council (ERC) under the European Union’s Horizon 2020 research and innovation
  program (grant agreement 692692, AdG “GIANTSYN”) and the Fonds zur Förderung der
  Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein Award; P 36232-B, stand-alone
  grant), both to P.J."
article_processing_charge: No
article_type: review
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: 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, Jonas PM. Structure, biophysics, and circuit function of a “giant”
    cortical presynaptic terminal. <i>Science</i>. 2024;383(6687):eadg6757. doi:<a
    href="https://doi.org/10.1126/science.adg6757">10.1126/science.adg6757</a>
  apa: Vandael, D. H., &#38; Jonas, P. M. (2024). Structure, biophysics, and circuit
    function of a “giant” cortical presynaptic terminal. <i>Science</i>. AAAS. <a
    href="https://doi.org/10.1126/science.adg6757">https://doi.org/10.1126/science.adg6757</a>
  chicago: Vandael, David H, and Peter M Jonas. “Structure, Biophysics, and Circuit
    Function of a ‘Giant’ Cortical Presynaptic Terminal.” <i>Science</i>. AAAS, 2024.
    <a href="https://doi.org/10.1126/science.adg6757">https://doi.org/10.1126/science.adg6757</a>.
  ieee: D. H. Vandael and P. M. Jonas, “Structure, biophysics, and circuit function
    of a ‘giant’ cortical presynaptic terminal,” <i>Science</i>, vol. 383, no. 6687.
    AAAS, p. eadg6757, 2024.
  ista: Vandael DH, Jonas PM. 2024. Structure, biophysics, and circuit function of
    a ‘giant’ cortical presynaptic terminal. Science. 383(6687), eadg6757.
  mla: Vandael, David H., and Peter M. Jonas. “Structure, Biophysics, and Circuit
    Function of a ‘Giant’ Cortical Presynaptic Terminal.” <i>Science</i>, vol. 383,
    no. 6687, AAAS, 2024, p. eadg6757, doi:<a href="https://doi.org/10.1126/science.adg6757">10.1126/science.adg6757</a>.
  short: D.H. Vandael, P.M. Jonas, Science 383 (2024) eadg6757.
corr_author: '1'
date_created: 2024-03-17T23:00:57Z
date_published: 2024-03-08T00:00:00Z
date_updated: 2025-09-04T13:04:34Z
day: '08'
department:
- _id: PeJo
doi: 10.1126/science.adg6757
ec_funded: 1
external_id:
  isi:
  - '001216996700015'
  pmid:
  - '38452088'
intvolume: '       383'
isi: 1
issue: '6687'
language:
- iso: eng
month: '03'
oa_version: None
page: eadg6757
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: bd88be38-d553-11ed-ba76-81d5a70a6ef5
  grant_number: P36232
  name: Mechanisms of GABA release in hippocampal circuits
publication: Science
publication_identifier:
  eissn:
  - 1095-9203
publication_status: published
publisher: AAAS
quality_controlled: '1'
scopus_import: '1'
status: public
title: Structure, biophysics, and circuit function of a "giant" cortical presynaptic
  terminal
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 383
year: '2024'
...
---
_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'
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  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
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
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'
...
---
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: '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:
  isi:
  - '000650528700003'
  pmid:
  - '33990799'
file:
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month: '06'
oa: 1
oa_version: Submitted Version
page: 2947–2967
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: Nature Protocols
publication_identifier:
  eissn:
  - 1750-2799
  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'
...
---
_id: '9437'
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: 2026-04-29T22:30:40Z
day: '29'
ddc:
- '570'
department:
- _id: RySh
- _id: PeJo
doi: 10.7554/ELIFE.68274
ec_funded: 1
external_id:
  isi:
  - '000651761700001'
  pmid:
  - '33913808'
file:
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  success: 1
file_date_updated: 2021-05-31T09:43:09Z
has_accepted_license: '1'
intvolume: '        10'
isi: 1
language:
- iso: eng
month: '04'
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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    url: https://doi.org/10.1101/2020.04.16.045112
  record:
  - id: '19271'
    relation: dissertation_contains
    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'
  file_name: 2020_Neuron_Vandael.pdf
  file_size: 4390833
  relation: main_file
  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
    (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: '320'
abstract:
- lang: eng
  text: 'Fast-spiking, parvalbumin-expressing GABAergic interneurons (PV+-BCs) express
    a complex machinery of rapid signaling mechanisms, including specialized voltage-gated
    ion channels to generate brief action potentials (APs). However, short APs are
    associated with overlapping Na+ and K+ fluxes and are therefore energetically
    expensive. How the potentially vicious combination of high AP frequency and inefficient
    spike generation can be reconciled with limited energy supply is presently unclear.
    To address this question, we performed direct recordings from the PV+-BC axon,
    the subcellular structure where active conductances for AP initiation and propagation
    are located. Surprisingly, the energy required for the AP was, on average, only
    ∼1.6 times the theoretical minimum. High energy efficiency emerged from the combination
    of fast inactivation of Na+ channels and delayed activation of Kv3-type K+ channels,
    which minimized ion flux overlap during APs. Thus, the complementary tuning of
    axonal Na+ and K+ channel gating optimizes both fast signaling properties and
    metabolic efficiency. Hu et al. demonstrate that action potentials in parvalbumin-expressing
    GABAergic interneuron axons are energetically efficient, which is highly unexpected
    given their brief duration. High energy efficiency emerges from the combination
    of fast inactivation of voltage-gated Na+ channels and delayed activation of Kv3
    channels in the axon. '
article_processing_charge: Yes (in subscription journal)
author:
- first_name: Hua
  full_name: Hu, Hua
  id: 4AC0145C-F248-11E8-B48F-1D18A9856A87
  last_name: Hu
- first_name: Fabian
  full_name: Roth, Fabian
  last_name: Roth
- 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: Hu H, Roth F, Vandael DH, Jonas PM. Complementary tuning of Na+ and K+ channel
    gating underlies fast and energy-efficient action potentials in GABAergic interneuron
    axons. <i>Neuron</i>. 2018;98(1):156-165. doi:<a href="https://doi.org/10.1016/j.neuron.2018.02.024">10.1016/j.neuron.2018.02.024</a>
  apa: Hu, H., Roth, F., Vandael, D. H., &#38; Jonas, P. M. (2018). Complementary
    tuning of Na+ and K+ channel gating underlies fast and energy-efficient action
    potentials in GABAergic interneuron axons. <i>Neuron</i>. Elsevier. <a href="https://doi.org/10.1016/j.neuron.2018.02.024">https://doi.org/10.1016/j.neuron.2018.02.024</a>
  chicago: Hu, Hua, Fabian Roth, David H Vandael, and Peter M Jonas. “Complementary
    Tuning of Na+ and K+ Channel Gating Underlies Fast and Energy-Efficient Action
    Potentials in GABAergic Interneuron Axons.” <i>Neuron</i>. Elsevier, 2018. <a
    href="https://doi.org/10.1016/j.neuron.2018.02.024">https://doi.org/10.1016/j.neuron.2018.02.024</a>.
  ieee: H. Hu, F. Roth, D. H. Vandael, and P. M. Jonas, “Complementary tuning of Na+
    and K+ channel gating underlies fast and energy-efficient action potentials in
    GABAergic interneuron axons,” <i>Neuron</i>, vol. 98, no. 1. Elsevier, pp. 156–165,
    2018.
  ista: Hu H, Roth F, Vandael DH, Jonas PM. 2018. Complementary tuning of Na+ and
    K+ channel gating underlies fast and energy-efficient action potentials in GABAergic
    interneuron axons. Neuron. 98(1), 156–165.
  mla: Hu, Hua, et al. “Complementary Tuning of Na+ and K+ Channel Gating Underlies
    Fast and Energy-Efficient Action Potentials in GABAergic Interneuron Axons.” <i>Neuron</i>,
    vol. 98, no. 1, Elsevier, 2018, pp. 156–65, doi:<a href="https://doi.org/10.1016/j.neuron.2018.02.024">10.1016/j.neuron.2018.02.024</a>.
  short: H. Hu, F. Roth, D.H. Vandael, P.M. Jonas, Neuron 98 (2018) 156–165.
corr_author: '1'
date_created: 2018-12-11T11:45:48Z
date_published: 2018-04-04T00:00:00Z
date_updated: 2025-04-15T08:29:04Z
day: '04'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1016/j.neuron.2018.02.024
ec_funded: 1
external_id:
  isi:
  - '000429192100016'
file:
- access_level: open_access
  checksum: 76070f3729f9c603e1080d0151aa2b11
  content_type: application/pdf
  creator: dernst
  date_created: 2018-12-17T10:37:50Z
  date_updated: 2020-07-14T12:46:03Z
  file_id: '5690'
  file_name: 2018_Neuron_Hu.pdf
  file_size: 3180444
  relation: main_file
file_date_updated: 2020-07-14T12:46:03Z
has_accepted_license: '1'
intvolume: '        98'
isi: 1
issue: '1'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: 156 - 165
project:
- _id: 25C0F108-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '268548'
  name: Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 25C26B1E-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P24909-B24
  name: Mechanisms of transmitter release at GABAergic synapses
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z00312
  name: Synaptic communication in neuronal microcircuits
publication: Neuron
publication_status: published
publisher: Elsevier
publist_id: '7545'
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/a-certain-type-of-neurons-is-more-energy-efficient-than-previously-assumed/
scopus_import: '1'
status: public
title: Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient
  action potentials in GABAergic interneuron axons
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: 98
year: '2018'
...
---
_id: '1062'
abstract:
- lang: eng
  text: Mouse chromaffin cells (MCCs) generate action potential (AP) firing that regulates
    the Ca2+‐dependent release of catecholamines (CAs). Recent findings indicate that
    MCCs possess a variety of spontaneous firing modes that span from the common ‘tonic‐irregular’
    to the less frequent ‘burst’ firing. This latter is evident in a small fraction
    of MCCs but occurs regularly when Nav1.3/1.7 channels are made less available
    or when the Slo1β2‐subunit responsible for BK channel inactivation is deleted.
    Burst firing causes large increases of Ca2+‐entry and potentiates CA release by
    ∼3.5‐fold and thus may be a key mechanism for regulating MCC function. With the
    aim to uncover a physiological role for burst‐firing we investigated the effects
    of acidosis on MCC activity. Lowering the extracellular pH (pHo) from 7.4 to 7.0
    and 6.6 induces cell depolarizations of 10–15 mV that generate repeated bursts.
    Bursts at pHo 6.6 lasted ∼330 ms, occurred at 1–2 Hz and caused an ∼7‐fold increase
    of CA cumulative release. Burst firing originates from the inhibition of the pH‐sensitive
    TASK‐1/TASK‐3 channels and from a 40% BK channel conductance reduction at pHo
    7.0. The same pHo had little or no effect on Nav, Cav, Kv and SK channels that
    support AP firing in MCCs. Burst firing of pHo 6.6 could be mimicked by mixtures
    of the TASK‐1 blocker A1899 (300 nm) and BK blocker paxilline (300 nm) and could
    be prevented by blocking L‐type channels by adding 3 μm nifedipine. Mixtures of
    the two blockers raised cumulative CA‐secretion even more than low pHo (∼12‐fold),
    showing that the action of protons on vesicle release is mainly a result of the
    ionic conductance changes that increase Ca2+‐entry during bursts. Our data provide
    direct evidence suggesting that MCCs respond to low pHo with sustained depolarization,
    burst firing and enhanced CA‐secretion, thus mimicking the physiological response
    of CCs to acute acidosis and hyperkalaemia generated during heavy exercise and
    muscle fatigue.
article_processing_charge: No
author:
- first_name: Laura
  full_name: Guarina, Laura
  last_name: Guarina
- 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: Valentina
  full_name: Carabelli, Valentina
  last_name: Carabelli
- first_name: Emilio
  full_name: Carbone, Emilio
  last_name: Carbone
citation:
  ama: Guarina L, Vandael DH, Carabelli V, Carbone E. Low pH inf o boosts burst firing
    and catecholamine release by blocking TASK-1 and BK channels while preserving
    Cav1 channels in mouse chromaffin cells. <i>Journal of Physiology</i>. 2017;595(8):2587-2609.
    doi:<a href="https://doi.org/10.1113/JP273735">10.1113/JP273735</a>
  apa: Guarina, L., Vandael, D. H., Carabelli, V., &#38; Carbone, E. (2017). Low pH
    inf o boosts burst firing and catecholamine release by blocking TASK-1 and BK
    channels while preserving Cav1 channels in mouse chromaffin cells. <i>Journal
    of Physiology</i>. Wiley-Blackwell. <a href="https://doi.org/10.1113/JP273735">https://doi.org/10.1113/JP273735</a>
  chicago: Guarina, Laura, David H Vandael, Valentina Carabelli, and Emilio Carbone.
    “Low PH Inf o Boosts Burst Firing and Catecholamine Release by Blocking TASK-1
    and BK Channels While Preserving Cav1 Channels in Mouse Chromaffin Cells.” <i>Journal
    of Physiology</i>. Wiley-Blackwell, 2017. <a href="https://doi.org/10.1113/JP273735">https://doi.org/10.1113/JP273735</a>.
  ieee: L. Guarina, D. H. Vandael, V. Carabelli, and E. Carbone, “Low pH inf o boosts
    burst firing and catecholamine release by blocking TASK-1 and BK channels while
    preserving Cav1 channels in mouse chromaffin cells,” <i>Journal of Physiology</i>,
    vol. 595, no. 8. Wiley-Blackwell, pp. 2587–2609, 2017.
  ista: Guarina L, Vandael DH, Carabelli V, Carbone E. 2017. Low pH inf o boosts burst
    firing and catecholamine release by blocking TASK-1 and BK channels while preserving
    Cav1 channels in mouse chromaffin cells. Journal of Physiology. 595(8), 2587–2609.
  mla: Guarina, Laura, et al. “Low PH Inf o Boosts Burst Firing and Catecholamine
    Release by Blocking TASK-1 and BK Channels While Preserving Cav1 Channels in Mouse
    Chromaffin Cells.” <i>Journal of Physiology</i>, vol. 595, no. 8, Wiley-Blackwell,
    2017, pp. 2587–609, doi:<a href="https://doi.org/10.1113/JP273735">10.1113/JP273735</a>.
  short: L. Guarina, D.H. Vandael, V. Carabelli, E. Carbone, Journal of Physiology
    595 (2017) 2587–2609.
date_created: 2018-12-11T11:49:56Z
date_published: 2017-04-15T00:00:00Z
date_updated: 2023-09-20T12:09:47Z
day: '15'
doi: 10.1113/JP273735
extern: '1'
external_id:
  isi:
  - '000399430300022'
intvolume: '       595'
isi: 1
issue: '8'
language:
- iso: eng
month: '04'
oa_version: None
page: '2587 - 2609 '
publication: Journal of Physiology
publication_status: published
publisher: Wiley-Blackwell
publist_id: '6326'
quality_controlled: '1'
status: public
title: Low pH inf o boosts burst firing and catecholamine release by blocking TASK-1
  and BK channels while preserving Cav1 channels in mouse chromaffin cells
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 595
year: '2017'
...
---
_id: '1845'
abstract:
- lang: eng
  text: Based on extrapolation from excitatory synapses, it is often assumed that
    depletion of the releasable pool of synaptic vesicles is the main factor underlying
    depression at inhibitory synapses. In this issue of Neuron, using subcellular
    patch-clamp recording from inhibitory presynaptic terminals, Kawaguchi and Sakaba
    (2015) show that at Purkinje cell-deep cerebellar nuclei neuron synapses, changes
    in presynaptic action potential waveform substantially contribute to synaptic
    depression. Based on extrapolation from excitatory synapses, it is often assumed
    that depletion of the releasable pool of synaptic vesicles is the main factor
    underlying depression at inhibitory synapses. In this issue of Neuron, using subcellular
    patch-clamp recording from inhibitory presynaptic terminals, Kawaguchi and Sakaba
    (2015) show that at Purkinje cell-deep cerebellar nuclei neuron synapses, changes
    in presynaptic action potential waveform substantially contribute to synaptic
    depression.
article_processing_charge: No
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: 'Claudia '
  full_name: 'Espinoza Martinez, Claudia '
  id: 31FFEE2E-F248-11E8-B48F-1D18A9856A87
  last_name: Espinoza Martinez
  orcid: 0000-0003-4710-2082
- 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, Espinoza Martinez C, Jonas PM. Excitement about inhibitory presynaptic
    terminals. <i>Neuron</i>. 2015;85(6):1149-1151. doi:<a href="https://doi.org/10.1016/j.neuron.2015.03.006">10.1016/j.neuron.2015.03.006</a>
  apa: Vandael, D. H., Espinoza Martinez, C., &#38; Jonas, P. M. (2015). Excitement
    about inhibitory presynaptic terminals. <i>Neuron</i>. Elsevier. <a href="https://doi.org/10.1016/j.neuron.2015.03.006">https://doi.org/10.1016/j.neuron.2015.03.006</a>
  chicago: Vandael, David H, Claudia  Espinoza Martinez, and Peter M Jonas. “Excitement
    about Inhibitory Presynaptic Terminals.” <i>Neuron</i>. Elsevier, 2015. <a href="https://doi.org/10.1016/j.neuron.2015.03.006">https://doi.org/10.1016/j.neuron.2015.03.006</a>.
  ieee: D. H. Vandael, C. Espinoza Martinez, and P. M. Jonas, “Excitement about inhibitory
    presynaptic terminals,” <i>Neuron</i>, vol. 85, no. 6. Elsevier, pp. 1149–1151,
    2015.
  ista: Vandael DH, Espinoza Martinez C, Jonas PM. 2015. Excitement about inhibitory
    presynaptic terminals. Neuron. 85(6), 1149–1151.
  mla: Vandael, David H., et al. “Excitement about Inhibitory Presynaptic Terminals.”
    <i>Neuron</i>, vol. 85, no. 6, Elsevier, 2015, pp. 1149–51, doi:<a href="https://doi.org/10.1016/j.neuron.2015.03.006">10.1016/j.neuron.2015.03.006</a>.
  short: D.H. Vandael, C. Espinoza Martinez, P.M. Jonas, Neuron 85 (2015) 1149–1151.
corr_author: '1'
date_created: 2018-12-11T11:54:19Z
date_published: 2015-03-18T00:00:00Z
date_updated: 2025-09-23T08:44:39Z
day: '18'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1016/j.neuron.2015.03.006
external_id:
  isi:
  - '000351319000002'
file:
- access_level: open_access
  checksum: d1808550e376a0eca2a950fda017cfa6
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:16:07Z
  date_updated: 2020-07-14T12:45:19Z
  file_id: '5192'
  file_name: IST-2017-822-v1+1_Perspective_Fig__Final.pdf
  file_size: 411832
  relation: main_file
- access_level: open_access
  checksum: a279f4ae61e6c8f33d68f69a0d02097d
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:16:07Z
  date_updated: 2020-07-14T12:45:19Z
  file_id: '5193'
  file_name: IST-2017-822-v1+2_Perspective_Final2.pdf
  file_size: 100769
  relation: main_file
file_date_updated: 2020-07-14T12:45:19Z
has_accepted_license: '1'
intvolume: '        85'
isi: 1
issue: '6'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: 1149 - 1151
publication: Neuron
publication_status: published
publisher: Elsevier
publist_id: '5256'
pubrep_id: '822'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Excitement about inhibitory presynaptic terminals
tmp:
  image: /images/cc_by_nc.png
  legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
  short: CC BY-NC (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 85
year: '2015'
...
---
_id: '1535'
abstract:
- lang: eng
  text: Neuronal and neuroendocrine L-type calcium channels (Cav1.2, Cav1.3) open
    readily at relatively low membrane potentials and allow Ca2+ to enter the cells
    near resting potentials. In this way, Cav1.2 and Cav1.3 shape the action potential
    waveform, contribute to gene expression, synaptic plasticity, neuronal differentiation,
    hormone secretion and pacemaker activity. In the chromaffin cells (CCs) of the
    adrenal medulla, Cav1.3 is highly expressed and is shown to support most of the
    pacemaking current that sustains action potential (AP) firings and part of the
    catecholamine secretion. Cav1.3 forms Ca2+-nanodomains with the fast inactivating
    BK channels and drives the resting SK currents. These latter set the inter-spike
    interval duration between consecutive spikes during spontaneous firing and the
    rate of spike adaptation during sustained depolarizations. Cav1.3 plays also a
    primary role in the switch from “tonic” to “burst” firing that occurs in mouse
    CCs when either the availability of voltage-gated Na channels (Nav) is reduced
    or the β2 subunit featuring the fast inactivating BK channels is deleted. Here,
    we discuss the functional role of these “neuronlike” firing modes in CCs and how
    Cav1.3 contributes to them. The open issue is to understand how these novel firing
    patterns are adapted to regulate the quantity of circulating catecholamines during
    resting condition or in response to acute and chronic stress.
acknowledgement: This work was supported by the Italian MIUR (PRIN 2010/2011 project
  2010JFYFY2) and the University of Torino.
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: Andrea
  full_name: Marcantoni, Andrea
  last_name: Marcantoni
- first_name: Emilio
  full_name: Carbone, Emilio
  last_name: Carbone
citation:
  ama: Vandael DH, Marcantoni A, Carbone E. Cav1.3 channels as key regulators of neuron-like
    firings and catecholamine release in chromaffin cells. <i>Current Molecular Pharmacology</i>.
    2015;8(2):149-161. doi:<a href="https://doi.org/10.2174/1874467208666150507105443">10.2174/1874467208666150507105443</a>
  apa: Vandael, D. H., Marcantoni, A., &#38; Carbone, E. (2015). Cav1.3 channels as
    key regulators of neuron-like firings and catecholamine release in chromaffin
    cells. <i>Current Molecular Pharmacology</i>. Bentham Science Publishers. <a href="https://doi.org/10.2174/1874467208666150507105443">https://doi.org/10.2174/1874467208666150507105443</a>
  chicago: Vandael, David H, Andrea Marcantoni, and Emilio Carbone. “Cav1.3 Channels
    as Key Regulators of Neuron-like Firings and Catecholamine Release in Chromaffin
    Cells.” <i>Current Molecular Pharmacology</i>. Bentham Science Publishers, 2015.
    <a href="https://doi.org/10.2174/1874467208666150507105443">https://doi.org/10.2174/1874467208666150507105443</a>.
  ieee: D. H. Vandael, A. Marcantoni, and E. Carbone, “Cav1.3 channels as key regulators
    of neuron-like firings and catecholamine release in chromaffin cells,” <i>Current
    Molecular Pharmacology</i>, vol. 8, no. 2. Bentham Science Publishers, pp. 149–161,
    2015.
  ista: Vandael DH, Marcantoni A, Carbone E. 2015. Cav1.3 channels as key regulators
    of neuron-like firings and catecholamine release in chromaffin cells. Current
    Molecular Pharmacology. 8(2), 149–161.
  mla: Vandael, David H., et al. “Cav1.3 Channels as Key Regulators of Neuron-like
    Firings and Catecholamine Release in Chromaffin Cells.” <i>Current Molecular Pharmacology</i>,
    vol. 8, no. 2, Bentham Science Publishers, 2015, pp. 149–61, doi:<a href="https://doi.org/10.2174/1874467208666150507105443">10.2174/1874467208666150507105443</a>.
  short: D.H. Vandael, A. Marcantoni, E. Carbone, Current Molecular Pharmacology 8
    (2015) 149–161.
date_created: 2018-12-11T11:52:35Z
date_published: 2015-10-01T00:00:00Z
date_updated: 2025-09-23T08:12:18Z
day: '01'
department:
- _id: PeJo
doi: 10.2174/1874467208666150507105443
external_id:
  isi:
  - '000217186100005'
  pmid:
  - '25966692'
intvolume: '         8'
isi: 1
issue: '2'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384372/
month: '10'
oa: 1
oa_version: Submitted Version
page: 149 - 161
pmid: 1
publication: Current Molecular Pharmacology
publication_status: published
publisher: Bentham Science Publishers
publist_id: '5636'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Cav1.3 channels as key regulators of neuron-like firings and catecholamine
  release in chromaffin cells
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 8
year: '2015'
...
---
_id: '1565'
abstract:
- lang: eng
  text: Leptin is an adipokine produced by the adipose tissue regulating body weight
    through its appetite-suppressing effect. Besides being expressed in the hypothalamus
    and hippocampus, leptin receptors (ObRs) are also present in chromaffin cells
    of the adrenal medulla. In the present study, we report the effect of leptin on
    mouse chromaffin cell (MCC) functionality, focusing on cell excitability and catecholamine
    secretion. Acute application of leptin (1 nm) on spontaneously firing MCCs caused
    a slowly developing membrane hyperpolarization followed by complete blockade of
    action potential (AP) firing. This inhibitory effect at rest was abolished by
    the BK channel blocker paxilline (1 μm), suggesting the involvement of BK potassium
    channels. Single-channel recordings in 'perforated microvesicles' confirmed that
    leptin increased BK channel open probability without altering its unitary conductance.
    BK channel up-regulation was associated with the phosphoinositide 3-kinase (PI3K)
    signalling cascade because the PI3K specific inhibitor wortmannin (100 nm) fully
    prevented BK current increase. We also tested the effect of leptin on evoked AP
    firing and Ca2+-driven exocytosis. Although leptin preserves well-adapted AP trains
    of lower frequency, APs are broader and depolarization-evoked exocytosis is increased
    as a result of the larger size of the ready-releasable pool and higher frequency
    of vesicle release. The kinetics and quantal size of single secretory events remained
    unaltered. Leptin had no effect on firing and secretion in db-/db- mice lacking
    the ObR gene, confirming its specificity. In conclusion, leptin exhibits a dual
    action on MCC activity. It dampens AP firing at rest but preserves AP firing and
    increases catecholamine secretion during sustained stimulation, highlighting the
    importance of the adipo-adrenal axis in the leptin-mediated increase of sympathetic
    tone and catecholamine release.
acknowledgement: "This work was supported by the Compagnia di San Paolo Foundation
  ‘Neuroscience Program’ to VC and ‘Progetto di Ateneo 2011-13’ to EC.\r\nWe thank
  Dr Claudio Franchino for cell preparation and for providing excellent technical
  support."
article_processing_charge: No
author:
- first_name: Daniela
  full_name: Gavello, Daniela
  last_name: Gavello
- 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: Sara
  full_name: Gosso, Sara
  last_name: Gosso
- first_name: Emilio
  full_name: Carbone, Emilio
  last_name: Carbone
- first_name: Valentina
  full_name: Carabelli, Valentina
  last_name: Carabelli
citation:
  ama: Gavello D, Vandael DH, Gosso S, Carbone E, Carabelli V. Dual action of leptin
    on rest-firing and stimulated catecholamine release via phosphoinositide 3-kinase-riven
    BK channel up-regulation in mouse chromaffin cells. <i>Journal of Physiology</i>.
    2015;593(22):4835-4853. doi:<a href="https://doi.org/10.1113/JP271078">10.1113/JP271078</a>
  apa: Gavello, D., Vandael, D. H., Gosso, S., Carbone, E., &#38; Carabelli, V. (2015).
    Dual action of leptin on rest-firing and stimulated catecholamine release via
    phosphoinositide 3-kinase-riven BK channel up-regulation in mouse chromaffin cells.
    <i>Journal of Physiology</i>. Wiley-Blackwell. <a href="https://doi.org/10.1113/JP271078">https://doi.org/10.1113/JP271078</a>
  chicago: Gavello, Daniela, David H Vandael, Sara Gosso, Emilio Carbone, and Valentina
    Carabelli. “Dual Action of Leptin on Rest-Firing and Stimulated Catecholamine
    Release via Phosphoinositide 3-Kinase-Riven BK Channel up-Regulation in Mouse
    Chromaffin Cells.” <i>Journal of Physiology</i>. Wiley-Blackwell, 2015. <a href="https://doi.org/10.1113/JP271078">https://doi.org/10.1113/JP271078</a>.
  ieee: D. Gavello, D. H. Vandael, S. Gosso, E. Carbone, and V. Carabelli, “Dual action
    of leptin on rest-firing and stimulated catecholamine release via phosphoinositide
    3-kinase-riven BK channel up-regulation in mouse chromaffin cells,” <i>Journal
    of Physiology</i>, vol. 593, no. 22. Wiley-Blackwell, pp. 4835–4853, 2015.
  ista: Gavello D, Vandael DH, Gosso S, Carbone E, Carabelli V. 2015. Dual action
    of leptin on rest-firing and stimulated catecholamine release via phosphoinositide
    3-kinase-riven BK channel up-regulation in mouse chromaffin cells. Journal of
    Physiology. 593(22), 4835–4853.
  mla: Gavello, Daniela, et al. “Dual Action of Leptin on Rest-Firing and Stimulated
    Catecholamine Release via Phosphoinositide 3-Kinase-Riven BK Channel up-Regulation
    in Mouse Chromaffin Cells.” <i>Journal of Physiology</i>, vol. 593, no. 22, Wiley-Blackwell,
    2015, pp. 4835–53, doi:<a href="https://doi.org/10.1113/JP271078">10.1113/JP271078</a>.
  short: D. Gavello, D.H. Vandael, S. Gosso, E. Carbone, V. Carabelli, Journal of
    Physiology 593 (2015) 4835–4853.
date_created: 2018-12-11T11:52:45Z
date_published: 2015-11-15T00:00:00Z
date_updated: 2025-09-23T08:30:00Z
day: '15'
department:
- _id: PeJo
doi: 10.1113/JP271078
external_id:
  isi:
  - '000365267700003'
  pmid:
  - '26282459'
intvolume: '       593'
isi: 1
issue: '22'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650409/
month: '11'
oa: 1
oa_version: Submitted Version
page: 4835 - 4853
pmid: 1
publication: Journal of Physiology
publication_status: published
publisher: Wiley-Blackwell
publist_id: '5606'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Dual action of leptin on rest-firing and stimulated catecholamine release via
  phosphoinositide 3-kinase-riven BK channel up-regulation in mouse chromaffin cells
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 593
year: '2015'
...
---
_id: '1580'
abstract:
- lang: eng
  text: Synapsins (Syns) are an evolutionarily conserved family of presynaptic proteins
    crucial for the fine-tuning of synaptic function. A large amount of experimental
    evidences has shown that Syns are involved in the development of epileptic phenotypes
    and several mutations in Syn genes have been associated with epilepsy in humans
    and animal models. Syn mutations induce alterations in circuitry and neurotransmitter
    release, differentially affecting excitatory and inhibitory synapses, thus causing
    an excitation/inhibition imbalance in network excitability toward hyperexcitability
    that may be a determinant with regard to the development of epilepsy. Another
    approach to investigate epileptogenic mechanisms is to understand how silencing
    Syn affects the cellular behavior of single neurons and is associated with the
    hyperexcitable phenotypes observed in epilepsy. Here, we examined the functional
    effects of antisense-RNA inhibition of Syn expression on individually identified
    and isolated serotonergic cells of the Helix land snail. We found that Helix synapsin
    silencing increases cell excitability characterized by a slightly depolarized
    resting membrane potential, decreases the rheobase, reduces the threshold for
    action potential (AP) firing and increases the mean and instantaneous firing rates,
    with respect to control cells. The observed increase of Ca2+ and BK currents in
    Syn-silenced cells seems to be related to changes in the shape of the AP waveform.
    These currents sustain the faster spiking in Syn-deficient cells by increasing
    the after hyperpolarization and limiting the Na+ and Ca2+ channel inactivation
    during repetitive firing. This in turn speeds up the depolarization phase by reaching
    the AP threshold faster. Our results provide evidence that Syn silencing increases
    intrinsic cell excitability associated with increased Ca2+ and Ca2+-dependent
    BK currents in the absence of excitatory or inhibitory inputs.
article_processing_charge: No
article_type: original
author:
- first_name: Oscar
  full_name: Brenes, Oscar
  last_name: Brenes
- 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: Emilio
  full_name: Carbone, Emilio
  last_name: Carbone
- first_name: Pier
  full_name: Montarolo, Pier
  last_name: Montarolo
- first_name: Mirella
  full_name: Ghirardi, Mirella
  last_name: Ghirardi
citation:
  ama: Brenes O, Vandael DH, Carbone E, Montarolo P, Ghirardi M. Knock-down of synapsin
    alters cell excitability and action potential waveform by potentiating BK and
    voltage gated Ca2 currents in Helix serotonergic neurons. <i>Neuroscience</i>.
    2015;311:430-443. doi:<a href="https://doi.org/10.1016/j.neuroscience.2015.10.046">10.1016/j.neuroscience.2015.10.046</a>
  apa: Brenes, O., Vandael, D. H., Carbone, E., Montarolo, P., &#38; Ghirardi, M.
    (2015). Knock-down of synapsin alters cell excitability and action potential waveform
    by potentiating BK and voltage gated Ca2 currents in Helix serotonergic neurons.
    <i>Neuroscience</i>. Elsevier. <a href="https://doi.org/10.1016/j.neuroscience.2015.10.046">https://doi.org/10.1016/j.neuroscience.2015.10.046</a>
  chicago: Brenes, Oscar, David H Vandael, Emilio Carbone, Pier Montarolo, and Mirella
    Ghirardi. “Knock-down of Synapsin Alters Cell Excitability and Action Potential
    Waveform by Potentiating BK and Voltage Gated Ca2 Currents in Helix Serotonergic
    Neurons.” <i>Neuroscience</i>. Elsevier, 2015. <a href="https://doi.org/10.1016/j.neuroscience.2015.10.046">https://doi.org/10.1016/j.neuroscience.2015.10.046</a>.
  ieee: O. Brenes, D. H. Vandael, E. Carbone, P. Montarolo, and M. Ghirardi, “Knock-down
    of synapsin alters cell excitability and action potential waveform by potentiating
    BK and voltage gated Ca2 currents in Helix serotonergic neurons,” <i>Neuroscience</i>,
    vol. 311. Elsevier, pp. 430–443, 2015.
  ista: Brenes O, Vandael DH, Carbone E, Montarolo P, Ghirardi M. 2015. Knock-down
    of synapsin alters cell excitability and action potential waveform by potentiating
    BK and voltage gated Ca2 currents in Helix serotonergic neurons. Neuroscience.
    311, 430–443.
  mla: Brenes, Oscar, et al. “Knock-down of Synapsin Alters Cell Excitability and
    Action Potential Waveform by Potentiating BK and Voltage Gated Ca2 Currents in
    Helix Serotonergic Neurons.” <i>Neuroscience</i>, vol. 311, Elsevier, 2015, pp.
    430–43, doi:<a href="https://doi.org/10.1016/j.neuroscience.2015.10.046">10.1016/j.neuroscience.2015.10.046</a>.
  short: O. Brenes, D.H. Vandael, E. Carbone, P. Montarolo, M. Ghirardi, Neuroscience
    311 (2015) 430–443.
date_created: 2018-12-11T11:52:50Z
date_published: 2015-12-17T00:00:00Z
date_updated: 2025-09-23T09:25:46Z
day: '17'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1016/j.neuroscience.2015.10.046
external_id:
  isi:
  - '000366144000037'
file:
- access_level: open_access
  checksum: af2c4c994718c7be417eba0dc746aac9
  content_type: application/pdf
  creator: dernst
  date_created: 2020-05-15T06:50:20Z
  date_updated: 2020-07-14T12:45:02Z
  file_id: '7849'
  file_name: 2015_Neuroscience_Brenes.pdf
  file_size: 5563015
  relation: main_file
file_date_updated: 2020-07-14T12:45:02Z
has_accepted_license: '1'
intvolume: '       311'
isi: 1
language:
- iso: eng
month: '12'
oa: 1
oa_version: Submitted Version
page: 430 - 443
publication: Neuroscience
publication_status: published
publisher: Elsevier
publist_id: '5591'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Knock-down of synapsin alters cell excitability and action potential waveform
  by potentiating BK and voltage gated Ca2 currents in Helix serotonergic neurons
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 311
year: '2015'
...
