---
_id: '21442'
author:
- first_name: Alois
full_name: Schlögl, Alois
id: 45BF87EE-F248-11E8-B48F-1D18A9856A87
last_name: Schlögl
orcid: 0000-0002-5621-8100
citation:
ama: Schlögl A. CA3Simu v1.06 (vargas2026v1). 2026. doi:10.15479/AT-ISTA-21442
apa: Schlögl, A. (2026). CA3Simu v1.06 (vargas2026v1). Institute of Science and
Technology Austria. https://doi.org/10.15479/AT-ISTA-21442
chicago: Schlögl, Alois. “CA3Simu v1.06 (Vargas2026v1).” Institute of Science and
Technology Austria, 2026. https://doi.org/10.15479/AT-ISTA-21442.
ieee: A. Schlögl, “CA3Simu v1.06 (vargas2026v1).” Institute of Science and Technology
Austria, 2026.
ista: Schlögl A. 2026. CA3Simu v1.06 (vargas2026v1), Institute of Science and Technology
Austria, 10.15479/AT-ISTA-21442.
mla: Schlögl, Alois. CA3Simu v1.06 (Vargas2026v1). Institute of Science and
Technology Austria, 2026, doi:10.15479/AT-ISTA-21442.
short: A. Schlögl, (2026).
corr_author: '1'
date_created: 2026-03-12T08:20:46Z
date_published: 2026-03-12T00:00:00Z
date_updated: 2026-03-12T11:28:52Z
day: '12'
department:
- _id: ScienComp
- _id: PeJo
doi: 10.15479/AT-ISTA-21442
ec_funded: 1
file:
- access_level: open_access
checksum: 441c8827717dcda05f91c127d15cf1e9
content_type: application/gzip
creator: schloegl
date_created: 2026-03-12T08:19:14Z
date_updated: 2026-03-12T08:19:14Z
file_id: '21443'
file_name: ca3simu-vargas2026v1.tar.gz
file_size: 160410
relation: main_file
success: 1
- access_level: open_access
checksum: 3c0092076228a15c0a7ae703192d43ea
content_type: text/markdown
creator: schloegl
date_created: 2026-03-12T10:24:45Z
date_updated: 2026-03-12T10:24:45Z
file_id: '21445'
file_name: README.md
file_size: 10923
relation: main_file
success: 1
file_date_updated: 2026-03-12T10:24:45Z
has_accepted_license: '1'
keyword:
- hypocampus
- ca3 simulations
- modelling
license: https://opensource.org/licenses/GPL-3.0
month: '03'
oa: 1
project:
- _id: e62b56fe-ab3c-11f0-94c7-d181dd352b3b
grant_number: '101199096'
name: Synaptic mechanisms of engram storage and retrieval in CA3 hippocampal microcircuits
- _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5
grant_number: P36232
name: Mechanisms of GABA release in hippocampal circuits
- _id: 8d9195e9-16d5-11f0-9cad-d075be887a1e
grant_number: PAT 4178023
name: Synaptic networks of human brain
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glutamatergic synapse
publisher: Institute of Science and Technology Austria
status: public
title: CA3Simu v1.06 (vargas2026v1)
tmp:
legal_code_url: https://www.gnu.org/licenses/gpl-3.0.en.html
name: GNU General Public License 3.0
short: GPL 3.0
type: software
user_id: 68b8ca59-c5b3-11ee-8790-cd641c68093d
year: '2026'
...
---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '20099'
abstract:
- lang: eng
text: The hippocampus, critical for learning and memory, is dogmatically described
as a trisynaptic circuit where dentate gyrus granule cells (GCs), CA3 pyramidal
neurons (PNs), and CA1 PNs are serially connected. However, CA3 also forms an
autoassociative network, and its PNs have diverse morphologies, intrinsic properties,
and GC input levels. How PN subtypes compose this recurrent network is unknown.
To determine the synaptic arrangement of identified CA3 PNs, we combine multicellular
patch-clamp recording and post hoc morphological analysis in mouse hippocampal
slices. PNs can be divided into distinct “superficial” and “deep” subclasses,
the latter including previously reported “athorny” cells. Subclasses have distinct
input-output transformations and asymmetric connectivity, which is more abundant
from superficial to deep PNs, splitting CA3 locally into two parallel recurrent
networks. Coincident spontaneous inhibition occurs frequently within but not between
subclasses, implying subclass-specific inhibitory innervation. Our results suggest
two separately controlled sublayers for parallel information processing in hippocampal
CA3.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: M-Shop
acknowledgement: We thank Andrea Navas-Olive and Rebecca J. Morse-Mora for critically
reading an earlier version of the manuscript. We also thank Florian Marr and Christina
Altmutter for excellent technical assistance, Alois Schlögl for programming and
data-handling assistance, Todor Asenov for technical support, and Eleftheria Kralli-Beller
for manuscript editing. This research was supported by the Scientific Services Units
(SSUs) of ISTA. We are particularly grateful for assistance from the Imaging and
Optics Facility, Preclinical Facility, Lab Support Facility, and Miba Machine Shop.
The project received funding from the European Research Council (ERC) under the
European Union’s Horizon 2020 research and innovation program (grant agreement no.
692692 to P.J., Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635
to J.F.W., and an ISTplus Fellowship through Marie Skłodowska-Curie grant agreement
no. 754411 to V.V.-B.), the Austrian Science Fund (P 36232-B, PAT 4178023, and Cluster
of Excellence 10.55776/COE16 to P.J.), and a CONACyT fellowship (289638 to V.V.-B.)
and was supported by a non-stipendiary EMBO fellowship (ALTF 756–2020 to J.F.W.).
article_number: '116080'
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: Victor M
full_name: Vargas Barroso, Victor M
id: 2F55A9DE-F248-11E8-B48F-1D18A9856A87
last_name: Vargas Barroso
- 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: Watson J, Vargas Barroso VM, Jonas PM. Cell-specific wiring routes information
flow through hippocampal CA3. Cell Reports. 2025;44(8). doi:10.1016/j.celrep.2025.116080
apa: Watson, J., Vargas Barroso, V. M., & Jonas, P. M. (2025). Cell-specific
wiring routes information flow through hippocampal CA3. Cell Reports. Elsevier.
https://doi.org/10.1016/j.celrep.2025.116080
chicago: Watson, Jake, Victor M Vargas Barroso, and Peter M Jonas. “Cell-Specific
Wiring Routes Information Flow through Hippocampal CA3.” Cell Reports.
Elsevier, 2025. https://doi.org/10.1016/j.celrep.2025.116080.
ieee: J. Watson, V. M. Vargas Barroso, and P. M. Jonas, “Cell-specific wiring routes
information flow through hippocampal CA3,” Cell Reports, vol. 44, no. 8.
Elsevier, 2025.
ista: Watson J, Vargas Barroso VM, Jonas PM. 2025. Cell-specific wiring routes information
flow through hippocampal CA3. Cell Reports. 44(8), 116080.
mla: Watson, Jake, et al. “Cell-Specific Wiring Routes Information Flow through
Hippocampal CA3.” Cell Reports, vol. 44, no. 8, 116080, Elsevier, 2025,
doi:10.1016/j.celrep.2025.116080.
short: J. Watson, V.M. Vargas Barroso, P.M. Jonas, Cell Reports 44 (2025).
corr_author: '1'
date_created: 2025-08-03T22:01:30Z
date_published: 2025-08-01T00:00:00Z
date_updated: 2025-09-30T14:12:02Z
day: '01'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1016/j.celrep.2025.116080
ec_funded: 1
external_id:
isi:
- '001544472300002'
file:
- access_level: open_access
checksum: 556ff9760661ecd23949d75031043b1f
content_type: application/pdf
creator: dernst
date_created: 2025-08-04T06:53:07Z
date_updated: 2025-08-04T06:53:07Z
file_id: '20106'
file_name: 2025_CellReports_Watson.pdf
file_size: 27695214
relation: main_file
success: 1
file_date_updated: 2025-08-04T06:53:07Z
has_accepted_license: '1'
intvolume: ' 44'
isi: 1
issue: '8'
language:
- iso: eng
month: '08'
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: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
- _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5
grant_number: P36232
name: Mechanisms of GABA release in hippocampal circuits
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
publication: Cell Reports
publication_identifier:
eissn:
- 2211-1247
issn:
- 2639-1856
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Cell-specific wiring routes information flow through hippocampal CA3
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 44
year: '2025'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '20457'
abstract:
- lang: eng
text: Patch-clamp recording of miniature postsynaptic currents (mPSCs, or ‘minis’)
is used extensively to investigate the functional properties of synapses. With
this approach, spontaneous synaptic transmission events are recorded in an attempt
to determine quantal synaptic parameters or the effect of synaptic manipulations.
However, at the majority of brain synapses these events are small, with many undetectable
due to recording noise. The effects of incomplete detection were well appreciated
in the early years of synaptic physiology analysis, but appear to be increasingly
forgotten. Here we sought to characterise the consequences of incomplete detection
on the interpretability of mini analysis, using simulated mPSC data to give full
control over event parameters. We demonstrate that commonly reported measures
such as mean event amplitude and frequency, are misrepresented by the loss of
undetected events. Probabilistic loss of small events results in detected event
amplitude distributions that appear biologically complete, yet do not reflect
the underlying synaptic properties. With both simulated and experimental datasets,
we demonstrate that specific changes in event amplitude are primarily detected
as changes in frequency, compromising classical biological interpretations. To
facilitate more robust data analysis and interpretation, we detail a means for
experimental estimation of the event detection limit and provide practical recommendations
for data analysis. Together, our study highlights how mini analysis is prone to
falsely reporting synaptic changes, raising awareness of these considerations,
and provides a framework for more robust data analysis and interpretation.
acknowledgement: This work was supported by Biological Services teams at both the
Laboratory of Molecular Biology and Ares facilities. The authors are very grateful
to Prof. Helmut Kessels and Dr. Hinze Ho for initial discussions that led to this
study, Dr. Andrew Penn for constructive feedback on the project, Xinyao Dou for
comments on the study, and Profs. Peter Jonas and Roger Nicoll for feedback on the
manuscript. Funding was provided by the Medical Research Council (MRC – MC_U105174197
to I.H.G.) and the European Union's Horizon 2020 programme through a Marie Skłodowska-Curie
Actions Individual Fellowship (MSCA-IF 101026635 to J.F.W.).
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Ingo H.
full_name: Greger, Ingo H.
last_name: Greger
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
citation:
ama: Greger IH, Watson J. ‘Mini analysis’ misrepresents changes in synaptic properties
due to incomplete event detection. Journal of Physiology. 2025;603(22):7189-7205.
doi:10.1113/JP288183
apa: Greger, I. H., & Watson, J. (2025). ‘Mini analysis’ misrepresents changes
in synaptic properties due to incomplete event detection. Journal of Physiology.
Wiley. https://doi.org/10.1113/JP288183
chicago: Greger, Ingo H., and Jake Watson. “‘Mini Analysis’ Misrepresents Changes
in Synaptic Properties Due to Incomplete Event Detection.” Journal of Physiology.
Wiley, 2025. https://doi.org/10.1113/JP288183.
ieee: I. H. Greger and J. Watson, “‘Mini analysis’ misrepresents changes in synaptic
properties due to incomplete event detection,” Journal of Physiology, vol.
603, no. 22. Wiley, pp. 7189–7205, 2025.
ista: Greger IH, Watson J. 2025. ‘Mini analysis’ misrepresents changes in synaptic
properties due to incomplete event detection. Journal of Physiology. 603(22),
7189–7205.
mla: Greger, Ingo H., and Jake Watson. “‘Mini Analysis’ Misrepresents Changes in
Synaptic Properties Due to Incomplete Event Detection.” Journal of Physiology,
vol. 603, no. 22, Wiley, 2025, pp. 7189–205, doi:10.1113/JP288183.
short: I.H. Greger, J. Watson, Journal of Physiology 603 (2025) 7189–7205.
corr_author: '1'
date_created: 2025-10-12T22:01:27Z
date_published: 2025-11-15T00:00:00Z
date_updated: 2026-01-05T13:13:32Z
day: '15'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1113/JP288183
ec_funded: 1
external_id:
isi:
- '001581924700001'
pmid:
- '41015537'
file:
- access_level: open_access
checksum: 3326e49795f44a7c51c16ecbcce58cde
content_type: application/pdf
creator: dernst
date_created: 2026-01-05T13:13:06Z
date_updated: 2026-01-05T13:13:06Z
file_id: '20949'
file_name: 2025_JourPhysiology_Greger.pdf
file_size: 10875254
relation: main_file
success: 1
file_date_updated: 2026-01-05T13:13:06Z
has_accepted_license: '1'
intvolume: ' 603'
isi: 1
issue: '22'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
page: 7189-7205
pmid: 1
project:
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
publication: Journal of Physiology
publication_identifier:
eissn:
- 1469-7793
issn:
- 0022-3751
publication_status: published
publisher: Wiley
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://github.com/jakefwatson/miniplace
scopus_import: '1'
status: public
title: ‘Mini analysis’ misrepresents changes in synaptic properties due to incomplete
event detection
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: 603
year: '2025'
...
---
OA_type: closed access
_id: '20532'
abstract:
- lang: eng
text: A unified mechanism directs synaptic vesicle release
acknowledgement: The author thanks P. Jonas for feedback on the manuscript and acknowledges
support from the European Union’s Horizon 2020 research and innovation program under
Marie Skłodowska-Curie grant agreement no. 101034413.
article_processing_charge: No
article_type: comment
author:
- first_name: Katharina
full_name: Lichter, Katharina
id: 39302e62-fcfc-11ec-8196-8b01447dbd3d
last_name: Lichter
orcid: 0000-0002-1485-0351
citation:
ama: Lichter K. Kiss, shrink, run. Science. 2025;390(6770):236-237. doi:10.1126/science.aec0091
apa: Lichter, K. (2025). Kiss, shrink, run. Science. AAAS. https://doi.org/10.1126/science.aec0091
chicago: Lichter, Katharina. “Kiss, Shrink, Run.” Science. AAAS, 2025. https://doi.org/10.1126/science.aec0091.
ieee: K. Lichter, “Kiss, shrink, run,” Science, vol. 390, no. 6770. AAAS,
pp. 236–237, 2025.
ista: Lichter K. 2025. Kiss, shrink, run. Science. 390(6770), 236–237.
mla: Lichter, Katharina. “Kiss, Shrink, Run.” Science, vol. 390, no. 6770,
AAAS, 2025, pp. 236–37, doi:10.1126/science.aec0091.
short: K. Lichter, Science 390 (2025) 236–237.
corr_author: '1'
date_created: 2025-10-26T23:01:34Z
date_published: 2025-10-16T00:00:00Z
date_updated: 2025-12-01T15:04:34Z
day: '16'
department:
- _id: PeJo
doi: 10.1126/science.aec0091
ec_funded: 1
external_id:
isi:
- '001610669900024'
pmid:
- '41100630'
intvolume: ' 390'
isi: 1
issue: '6770'
language:
- iso: eng
month: '10'
oa_version: None
page: 236-237
pmid: 1
project:
- _id: fc2ed2f7-9c52-11eb-aca3-c01059dda49c
call_identifier: H2020
grant_number: '101034413'
name: 'IST-BRIDGE: International postdoctoral program'
publication: Science
publication_identifier:
eissn:
- 1095-9203
issn:
- 0036-8075
publication_status: published
publisher: AAAS
quality_controlled: '1'
scopus_import: '1'
status: public
title: Kiss, shrink, run
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 390
year: '2025'
...
---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '20977'
abstract:
- lang: eng
text: Hippocampal sharp-wave ripples (SPW-Rs) are high-frequency oscillations critical
for memory consolidation. Despite extensive characterization in rodents, their
detection in humans is limited by coarse spatial sampling, interictal epileptiform
discharges (IEDs), and a lack of consensus on human ripple localization and morphology.
Here, we demonstrate that mouse and human hippocampal ripples share spatial, spectral
and temporal features, which are clearly distinct from IEDs. In recordings from
male APP/PS1 mice, SPW-Rs were distinguishable from IEDs by multiple criteria.
Hippocampal ripples recorded during NREM sleep in female and male surgical epilepsy
patients exhibited similar narrowband frequency peaks and multiple ripple cycles
in the CA1 and subiculum regions. Conversely, IEDs showed a broad spatial extent
and wide-band frequency power. We developed a semi-automated, ripple curation
toolbox (ripmap) to separate event waveforms by low-dimensional embedding to reduce
false-positive rate in selected ripple channels. Our approach improves ripple
detection and provides a firm foundation for future human memory research.
acknowledgement: We thank Karl Rössler and Sebastian Brandner for the human SEEG implantations;
Katja Kobow for providing the histopathological findings of the patients; Jay Jeschke
for help with human electrode localization; Esha Brahmbhatt and Deren Aykan for
help with animal habituation; Mursel Karadas for the rodent treadmill design; Nicholas
Paleologos, Noam Nitzan, Michael D Hadler and Samuel McKenzie for rating events
in a human ripple survey included in a previous version of the manuscript; Nicholas
Paleologos for sharing NYU iEEG data for validating UMAP parameters; Julio Esparza
for help on the topological analysis through discussions; Thomas Hainmüller, Yiyao
Zhang and Mursel Karadas for feedback on the manuscript. We would like to acknowledge
Corticale SRL (Genoa, Italy) for providing the SiNAPS probes, and NeuroNexus (Ann
Arbor, MI) for their contribution of the data acquisition system and Radiens software.
We further acknowledge both Corticale and NeuroNexus for training and support making
this research possible. This work was supported by the German Research Foundation
(DFG; Walter Benjamin Fellowship MA 10301/1-1, A.M.), NYU Langone Health Finding
a Cure for Epilepsy and Seizures (FACES, A.M.), the NOMIS Fellowship (A.N.-O.),
the National Institutes of Health (R01NS127954, K23NS104252, A.L.; MH122391, U19NS107616,
R01MH139216 G.B.,), and the NYU Department of Neurology (A.L.).
article_number: '11636'
article_processing_charge: Yes
article_type: original
author:
- first_name: Anna
full_name: Maslarova, Anna
last_name: Maslarova
- first_name: Jiyun N.
full_name: Shin, Jiyun N.
last_name: Shin
- first_name: Andrea C
full_name: Navas Olivé, Andrea C
id: 739d26c9-52e8-11ee-8d72-f14d3893b4ce
last_name: Navas Olivé
orcid: 0000-0002-9280-8597
- first_name: Mihály
full_name: Vöröslakos, Mihály
last_name: Vöröslakos
- first_name: Hajo
full_name: Hamer, Hajo
last_name: Hamer
- first_name: Arnd
full_name: Doerfler, Arnd
last_name: Doerfler
- first_name: Simon
full_name: Henin, Simon
last_name: Henin
- first_name: György
full_name: Buzsáki, György
last_name: Buzsáki
- first_name: Anli
full_name: Liu, Anli
last_name: Liu
citation:
ama: Maslarova A, Shin JN, Navas Olivé AC, et al. Spatiotemporal patterns differentiate
hippocampal sharp-wave ripples from interictal epileptiform discharges in mice
and humans. Nature Communications. 2025;16. doi:10.1038/s41467-025-66562-6
apa: Maslarova, A., Shin, J. N., Navas Olivé, A. C., Vöröslakos, M., Hamer, H.,
Doerfler, A., … Liu, A. (2025). Spatiotemporal patterns differentiate hippocampal
sharp-wave ripples from interictal epileptiform discharges in mice and humans.
Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-025-66562-6
chicago: Maslarova, Anna, Jiyun N. Shin, Andrea C Navas Olivé, Mihály Vöröslakos,
Hajo Hamer, Arnd Doerfler, Simon Henin, György Buzsáki, and Anli Liu. “Spatiotemporal
Patterns Differentiate Hippocampal Sharp-Wave Ripples from Interictal Epileptiform
Discharges in Mice and Humans.” Nature Communications. Springer Nature,
2025. https://doi.org/10.1038/s41467-025-66562-6.
ieee: A. Maslarova et al., “Spatiotemporal patterns differentiate hippocampal
sharp-wave ripples from interictal epileptiform discharges in mice and humans,”
Nature Communications, vol. 16. Springer Nature, 2025.
ista: Maslarova A, Shin JN, Navas Olivé AC, Vöröslakos M, Hamer H, Doerfler A, Henin
S, Buzsáki G, Liu A. 2025. Spatiotemporal patterns differentiate hippocampal sharp-wave
ripples from interictal epileptiform discharges in mice and humans. Nature Communications.
16, 11636.
mla: Maslarova, Anna, et al. “Spatiotemporal Patterns Differentiate Hippocampal
Sharp-Wave Ripples from Interictal Epileptiform Discharges in Mice and Humans.”
Nature Communications, vol. 16, 11636, Springer Nature, 2025, doi:10.1038/s41467-025-66562-6.
short: A. Maslarova, J.N. Shin, A.C. Navas Olivé, M. Vöröslakos, H. Hamer, A. Doerfler,
S. Henin, G. Buzsáki, A. Liu, Nature Communications 16 (2025).
date_created: 2026-01-11T23:01:35Z
date_published: 2025-12-30T00:00:00Z
date_updated: 2026-01-12T09:31:56Z
day: '30'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1038/s41467-025-66562-6
external_id:
pmid:
- '39975118'
file:
- access_level: open_access
checksum: a8a1670e197484382e087be60f643945
content_type: application/pdf
creator: dernst
date_created: 2026-01-12T09:30:15Z
date_updated: 2026-01-12T09:30:15Z
file_id: '20978'
file_name: 2025_NatureComm_Maslarova.pdf
file_size: 7629997
relation: main_file
success: 1
file_date_updated: 2026-01-12T09:30:15Z
has_accepted_license: '1'
intvolume: ' 16'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 9B861AAC-BA93-11EA-9121-9846C619BF3A
name: NOMIS Fellowship Program
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Spatiotemporal patterns differentiate hippocampal sharp-wave ripples from interictal
epileptiform discharges in mice and humans
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: 16
year: '2025'
...
---
OA_place: publisher
OA_type: hybrid
_id: '18879'
abstract:
- lang: eng
text: 'Our brain has remarkable computational power, generating sophisticated behaviors,
storing memories over an individual’s lifetime, and producing higher cognitive
functions. However, little of our neuroscience knowledge covers the human brain.
Is this organ truly unique, or is it a scaled version of the extensively studied
rodent brain? Combining multicellular patch-clamp recording with expansion-based
superresolution microscopy and full-scale modeling, we determined the cellular
and microcircuit properties of the human hippocampal CA3 region, a fundamental
circuit for memory storage. In contrast to neocortical networks, human hippocampal
CA3 displayed sparse connectivity, providing a circuit architecture that maximizes
associational power. Human synapses showed unique reliability, high precision,
and long integration times, exhibiting both species- and circuit-specific properties.
Together with expanded neuronal numbers, these circuit characteristics greatly
enhanced the memory storage capacity of CA3. Our results reveal distinct microcircuit
properties of the human hippocampus and begin to unravel the inner workings of
our most complex organ. '
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: M-Shop
- _id: ScienComp
acknowledgement: We thank Florian Marr for excellent technical assistance, Christina
Altmutter and Julia Flor for technical support, Alois Schlögl for programming, Todor
Asenov for development of the transportation box for human brain tissue, Tim Vogels
for guidance on simulations, Marcus Huber for mathematical advice, Walter Kaufmann
for assistance with handling frozen tissue, and Eleftheria Kralli-Beller for manuscript
editing. This research was supported by the Scientific Services Units (SSUs) of
ISTA, and we are grateful for assistance from Christoph Sommer and the Imaging and
Optics Facility, Preclinical Facility, Lab Support Facility, Miba Machine Shop,
and Scientific Computing. We are particularly grateful to the patient donors for
their support of this project and also acknowledge the excellent support of the
Medical University of Vienna Department of Neurosurgery staff; Romana Hoeftberger
and the Division of Neuropathology and Neurochemistry; Gregor Kasprian and the Division
of Neuroradiology and Musculoskeletal Radiology; and Christoph Baumgartner, Martha
Feucht, and Ekaterina Pataraia for their clinical care of the patients included
in this study. We thank Laura Jonkman, the NABCA biobank, and postmortem brain sample
donors for their support of this research. The project received funding from the
European Research Council (ERC) under the European Union’s Horizon 2020 research
and innovation programme (advanced grant no. 692692 to P.J. and Marie Skłodowska-Curie
Actions Individual Fellowship no. 101026635 to J.F.W.), the Austrian Science Fund
(FWF; grant PAT 4178023 to P.J. and grant DK W1232 to M.R.T. and J.G.D.), the Austrian
Academy of Sciences (DOC fellowship 26137 to M.R.T.), and a NOMIS-ISTA fellowship
(to A.N.-O.).
article_processing_charge: Yes (via OA deal)
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: Victor M
full_name: Vargas Barroso, Victor M
id: 2F55A9DE-F248-11E8-B48F-1D18A9856A87
last_name: Vargas Barroso
- first_name: Rebecca
full_name: Morse, Rebecca
id: ceb89ae7-dc8d-11ea-abe3-da3301d0eab4
last_name: Morse
- first_name: Andrea C
full_name: Navas Olivé, Andrea C
id: 739d26c9-52e8-11ee-8d72-f14d3893b4ce
last_name: Navas Olivé
orcid: 0000-0002-9280-8597
- first_name: Mojtaba
full_name: Tavakoli, Mojtaba
id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
last_name: Tavakoli
orcid: 0000-0002-7667-6854
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
- first_name: Matthias
full_name: Tomschik, Matthias
last_name: Tomschik
- first_name: Karl
full_name: Rössler, Karl
last_name: Rössler
- 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: Watson J, Vargas Barroso VM, Morse R, et al. Human hippocampal CA3 uses specific
functional connectivity rules for efficient associative memory. Cell. 2025;188(2):501-514.e18.
doi:10.1016/j.cell.2024.11.022
apa: Watson, J., Vargas Barroso, V. M., Morse, R., Navas Olivé, A. C., Tavakoli,
M., Danzl, J. G., … Jonas, P. M. (2025). Human hippocampal CA3 uses specific functional
connectivity rules for efficient associative memory. Cell. Elsevier. https://doi.org/10.1016/j.cell.2024.11.022
chicago: Watson, Jake, Victor M Vargas Barroso, Rebecca Morse, Andrea C Navas Olivé,
Mojtaba Tavakoli, Johann G Danzl, Matthias Tomschik, Karl Rössler, and Peter M
Jonas. “Human Hippocampal CA3 Uses Specific Functional Connectivity Rules for
Efficient Associative Memory.” Cell. Elsevier, 2025. https://doi.org/10.1016/j.cell.2024.11.022.
ieee: J. Watson et al., “Human hippocampal CA3 uses specific functional connectivity
rules for efficient associative memory,” Cell, vol. 188, no. 2. Elsevier,
p. 501–514.e18, 2025.
ista: Watson J, Vargas Barroso VM, Morse R, Navas Olivé AC, Tavakoli M, Danzl JG,
Tomschik M, Rössler K, Jonas PM. 2025. Human hippocampal CA3 uses specific functional
connectivity rules for efficient associative memory. Cell. 188(2), 501–514.e18.
mla: Watson, Jake, et al. “Human Hippocampal CA3 Uses Specific Functional Connectivity
Rules for Efficient Associative Memory.” Cell, vol. 188, no. 2, Elsevier,
2025, p. 501–514.e18, doi:10.1016/j.cell.2024.11.022.
short: J. Watson, V.M. Vargas Barroso, R. Morse, A.C. Navas Olivé, M. Tavakoli,
J.G. Danzl, M. Tomschik, K. Rössler, P.M. Jonas, Cell 188 (2025) 501–514.e18.
corr_author: '1'
date_created: 2025-01-26T23:01:49Z
date_published: 2025-01-23T00:00:00Z
date_updated: 2026-04-14T08:34:32Z
day: '23'
ddc:
- '570'
department:
- _id: JoDa
- _id: PeJo
- _id: GradSch
doi: 10.1016/j.cell.2024.11.022
ec_funded: 1
external_id:
isi:
- '001408395600001'
pmid:
- '39667938'
file:
- access_level: open_access
checksum: d5a818edc32d249cdf75e1bb5b70a4b7
content_type: application/pdf
creator: dernst
date_created: 2025-01-27T08:46:33Z
date_updated: 2025-01-27T08:46:33Z
file_id: '18884'
file_name: 2025_Cell_Watson.pdf
file_size: 14082343
relation: main_file
success: 1
file_date_updated: 2025-01-27T08:46:33Z
has_accepted_license: '1'
intvolume: ' 188'
isi: 1
issue: '2'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: 501-514.e18
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: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
- _id: 6285a163-2b32-11ec-9570-8e204ca2dba5
grant_number: '26137'
name: Studying Organelle Structure and Function at Nanoscale Resolution with Expansion
Microscopy
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232
name: Molecular Drug Targets
- _id: 8d9195e9-16d5-11f0-9cad-d075be887a1e
grant_number: PAT 4178023
name: Synaptic networks of human brain
- _id: 9B861AAC-BA93-11EA-9121-9846C619BF3A
name: NOMIS Fellowship Program
publication: Cell
publication_identifier:
eissn:
- 1097-4172
issn:
- 0092-8674
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
record:
- id: '18688'
relation: earlier_version
status: public
scopus_import: '1'
status: public
title: Human hippocampal CA3 uses specific functional connectivity rules for efficient
associative memory
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: 188
year: '2025'
...
---
_id: '18058'
abstract:
- lang: eng
text: DNA cloning is a core technique in biomedical and biotechnological research
and is used to assemble and modify DNA fragments at will. While DNA cloning has
traditionally relied on restriction enzymes, recent homology-based methods offer
improved protocols together with seamless and directional assembly of desired
products, overcoming the main disadvantages of restriction enzyme DNA cloning.
This chapter provides a historical perspective on DNA cloning, presents a detailed
discussion on state-of-the-art in vitro and in vivo homology-based methodologies,
covering the basics of how to perform all major plasmid modifications (sub-cloning,
site-directed mutagenesis, insertions, and deletions), and gives examples of how
to apply these techniques for complex DNA cloning projects.
article_processing_charge: No
author:
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Sandra
full_name: Arroyo-Urea, Sandra
last_name: Arroyo-Urea
- first_name: Javier
full_name: García-Nafría, Javier
last_name: García-Nafría
citation:
ama: 'Watson J, Arroyo-Urea S, García-Nafría J. DNA Cloning. In: Liu D, ed. Handbook
of Molecular Biotechnology. 1st ed. Boca Raton: CRC Press; 2024:66-72. doi:10.1201/9781003055211-8'
apa: 'Watson, J., Arroyo-Urea, S., & García-Nafría, J. (2024). DNA Cloning.
In D. Liu (Ed.), Handbook of Molecular Biotechnology (1st ed., pp. 66–72).
Boca Raton: CRC Press. https://doi.org/10.1201/9781003055211-8'
chicago: 'Watson, Jake, Sandra Arroyo-Urea, and Javier García-Nafría. “DNA Cloning.”
In Handbook of Molecular Biotechnology, edited by Dongyou Liu, 1st ed.,
66–72. Boca Raton: CRC Press, 2024. https://doi.org/10.1201/9781003055211-8.'
ieee: 'J. Watson, S. Arroyo-Urea, and J. García-Nafría, “DNA Cloning,” in Handbook
of Molecular Biotechnology, 1st ed., D. Liu, Ed. Boca Raton: CRC Press, 2024,
pp. 66–72.'
ista: 'Watson J, Arroyo-Urea S, García-Nafría J. 2024.DNA Cloning. In: Handbook
of Molecular Biotechnology. , 66–72.'
mla: Watson, Jake, et al. “DNA Cloning.” Handbook of Molecular Biotechnology,
edited by Dongyou Liu, 1st ed., CRC Press, 2024, pp. 66–72, doi:10.1201/9781003055211-8.
short: J. Watson, S. Arroyo-Urea, J. García-Nafría, in:, D. Liu (Ed.), Handbook
of Molecular Biotechnology, 1st ed., CRC Press, Boca Raton, 2024, pp. 66–72.
date_created: 2024-09-11T10:40:36Z
date_published: 2024-09-05T00:00:00Z
date_updated: 2024-09-11T11:16:58Z
day: '05'
department:
- _id: PeJo
doi: 10.1201/9781003055211-8
edition: '1'
editor:
- first_name: Dongyou
full_name: Liu, Dongyou
last_name: Liu
language:
- iso: eng
month: '09'
oa_version: None
page: 66-72
place: Boca Raton
publication: Handbook of Molecular Biotechnology
publication_identifier:
eisbn:
- '9781003055211'
publication_status: published
publisher: CRC Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: DNA Cloning
type: book_chapter
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2024'
...
---
_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. Science. 2024;383(6687):eadg6757. doi:10.1126/science.adg6757
apa: Vandael, D. H., & Jonas, P. M. (2024). Structure, biophysics, and circuit
function of a “giant” cortical presynaptic terminal. Science. AAAS. https://doi.org/10.1126/science.adg6757
chicago: Vandael, David H, and Peter M Jonas. “Structure, Biophysics, and Circuit
Function of a ‘Giant’ Cortical Presynaptic Terminal.” Science. AAAS, 2024.
https://doi.org/10.1126/science.adg6757.
ieee: D. H. Vandael and P. M. Jonas, “Structure, biophysics, and circuit function
of a ‘giant’ cortical presynaptic terminal,” Science, 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.” Science, vol. 383,
no. 6687, AAAS, 2024, p. eadg6757, doi:10.1126/science.adg6757.
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'
...
---
OA_place: publisher
OA_type: hybrid
_id: '15379'
abstract:
- lang: eng
text: Long-term potentiation (LTP) of excitatory synapses is a leading model to
explain the concept of information storage in the brain. Multiple mechanisms contribute
to LTP, but central amongst them is an increased sensitivity of the postsynaptic
membrane to neurotransmitter release. This sensitivity is predominantly determined
by the abundance and localization of AMPA-type glutamate receptors (AMPARs). A
combination of AMPAR structural data, super-resolution imaging of excitatory synapses,
and an abundance of electrophysiological studies are providing an ever-clearer
picture of how AMPARs are recruited and organized at synaptic junctions. Here,
we review the latest insights into this process, and discuss how both cytoplasmic
and extracellular receptor elements cooperate to tune the AMPAR response at the
hippocampal CA1 synapse.
acknowledgement: The authors thank Alexander Scrutton and James M. Krieger for comments
on the manuscript. The authors also acknowledge Shraddha Nayak for help with Figure
1B design. This work was supported by grants from the Medical Research Council (MC_U105174197),
the BBSRC (BB/N002113/1), and the Wellcome Trust (223194/Z/21/Z) to IHG.
article_number: ' 2400006'
article_processing_charge: Yes (in subscription journal)
article_type: review
author:
- first_name: Imogen
full_name: Stockwell, Imogen
last_name: Stockwell
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Ingo H.
full_name: Greger, Ingo H.
last_name: Greger
citation:
ama: Stockwell I, Watson J, Greger IH. Tuning synaptic strength by regulation of
AMPA glutamate receptor localization. BioEssays. 2024;46(7). doi:10.1002/bies.202400006
apa: Stockwell, I., Watson, J., & Greger, I. H. (2024). Tuning synaptic strength
by regulation of AMPA glutamate receptor localization. BioEssays. Wiley.
https://doi.org/10.1002/bies.202400006
chicago: Stockwell, Imogen, Jake Watson, and Ingo H. Greger. “Tuning Synaptic Strength
by Regulation of AMPA Glutamate Receptor Localization.” BioEssays. Wiley,
2024. https://doi.org/10.1002/bies.202400006.
ieee: I. Stockwell, J. Watson, and I. H. Greger, “Tuning synaptic strength by regulation
of AMPA glutamate receptor localization,” BioEssays, vol. 46, no. 7. Wiley,
2024.
ista: Stockwell I, Watson J, Greger IH. 2024. Tuning synaptic strength by regulation
of AMPA glutamate receptor localization. BioEssays. 46(7), 2400006.
mla: Stockwell, Imogen, et al. “Tuning Synaptic Strength by Regulation of AMPA Glutamate
Receptor Localization.” BioEssays, vol. 46, no. 7, 2400006, Wiley, 2024,
doi:10.1002/bies.202400006.
short: I. Stockwell, J. Watson, I.H. Greger, BioEssays 46 (2024).
date_created: 2024-05-12T22:01:02Z
date_published: 2024-07-01T00:00:00Z
date_updated: 2025-09-08T07:25:02Z
day: '01'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1002/bies.202400006
external_id:
isi:
- '001214545700001'
pmid:
- '38693811'
file:
- access_level: open_access
checksum: dc8be74156657e8aab12a9d613233ee3
content_type: application/pdf
creator: dernst
date_created: 2025-01-09T09:31:05Z
date_updated: 2025-01-09T09:31:05Z
file_id: '18801'
file_name: 2024_BioEssays_Stockwell.pdf
file_size: 775825
relation: main_file
success: 1
file_date_updated: 2025-01-09T09:31:05Z
has_accepted_license: '1'
intvolume: ' 46'
isi: 1
issue: '7'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
publication: BioEssays
publication_identifier:
eissn:
- 1521-1878
issn:
- 0265-9247
publication_status: published
publisher: Wiley
quality_controlled: '1'
scopus_import: '1'
status: public
title: Tuning synaptic strength by regulation of AMPA glutamate receptor localization
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 46
year: '2024'
...
---
_id: '17122'
abstract:
- lang: eng
text: "Background: Motor alterations and lowered physical activity are common in
affective disorders. Previous research has indicated a link between depressive
symptoms and declining muscle strength primarily focusing on the elderly but not
younger individuals. Thus, we aimed to evaluate the relationship between mood
and muscle strength in a sample of N = 73 young to middle-aged hospitalized patients
(18–49 years, mean age 30.7 years) diagnosed with major depressive, bipolar and
schizoaffective disorder, with a focus on moderating effects of psychopharmacotherapy.
The study was carried out as a prospective observational study at a German psychiatric
university hospital between September 2021 and March 2022.\r\nMethods: Employing
a standardized strength circuit consisting of computerized strength training devices,
we measured the maximal muscle strength (Fmax) using three repetitions maximum
across four muscle regions (abdomen, arm, back, leg) at three time points (t1-t3)
over four weeks accompanied by psychometric testing (MADRS, BPRS, YRMS) and blood
lipid profiling in a clinical setting. For analysis of psychopharmacotherapy,
medication was split into activating (AM) and inhibiting (IM) medication and dosages
were normalized by the respective WHO defined daily dose.\r\nResults: While we
observed a significant decrease of the MADRS score and increase of the relative
total Fmax (rTFmax) in the first two weeks (t1-t2) but not later (both p < .001),
we did not reveal a significant bivariate correlation between disease severity
(MADRS) and muscle strength (rTFmax) at any of the timepoints. Individuals with
longer disease history displayed reduced rTFmax (p = .048). IM was significantly
associated with decreased rTFmax (p = .032). Regression models provide a more
substantial effect of gender, age, and IM on muscle strength than the depressive
episode itself (p < .001).\r\nConclusions: The results of the study indicate that
disease severity and muscle strength are not associated in young to middle-aged
inpatients with affective disorders using a strength circuit as observational
measurement. Future research will be needed to differentiate the effect of medication,
gender, and age on muscle strength and to develop interventions for prevention
of muscle weakness, especially in younger patients with chronic affective illnesses."
acknowledgement: "This work was supported by the project ‘Fellows Ride’ of the Thomas
Lurz und Dieter Schneider Stiftung and by the ‘Würzburger Bündnis gegen Depression’
(to S.K.-S).\r\nOpen Access funding enabled and organized by Projekt DEAL."
article_number: '401'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Hannah
full_name: Ramming, Hannah
last_name: Ramming
- first_name: Linda
full_name: Theuerkauf, Linda
last_name: Theuerkauf
- first_name: Olaf
full_name: Hoos, Olaf
last_name: Hoos
- first_name: Katharina
full_name: Lichter, Katharina
id: 39302e62-fcfc-11ec-8196-8b01447dbd3d
last_name: Lichter
orcid: 0000-0002-1485-0351
- first_name: Sarah
full_name: Kittel-Schneider, Sarah
last_name: Kittel-Schneider
citation:
ama: Ramming H, Theuerkauf L, Hoos O, Lichter K, Kittel-Schneider S. The association
between maximal muscle strength, disease severity and psychopharmacotherapy among
young to middle-aged inpatients with affective disorders – a prospective pilot
study. BMC Psychiatry. 2024;24. doi:10.1186/s12888-024-05849-2
apa: Ramming, H., Theuerkauf, L., Hoos, O., Lichter, K., & Kittel-Schneider,
S. (2024). The association between maximal muscle strength, disease severity and
psychopharmacotherapy among young to middle-aged inpatients with affective disorders
– a prospective pilot study. BMC Psychiatry. Springer Nature. https://doi.org/10.1186/s12888-024-05849-2
chicago: Ramming, Hannah, Linda Theuerkauf, Olaf Hoos, Katharina Lichter, and Sarah
Kittel-Schneider. “The Association between Maximal Muscle Strength, Disease Severity
and Psychopharmacotherapy among Young to Middle-Aged Inpatients with Affective
Disorders – a Prospective Pilot Study.” BMC Psychiatry. Springer Nature,
2024. https://doi.org/10.1186/s12888-024-05849-2.
ieee: H. Ramming, L. Theuerkauf, O. Hoos, K. Lichter, and S. Kittel-Schneider, “The
association between maximal muscle strength, disease severity and psychopharmacotherapy
among young to middle-aged inpatients with affective disorders – a prospective
pilot study,” BMC Psychiatry, vol. 24. Springer Nature, 2024.
ista: Ramming H, Theuerkauf L, Hoos O, Lichter K, Kittel-Schneider S. 2024. The
association between maximal muscle strength, disease severity and psychopharmacotherapy
among young to middle-aged inpatients with affective disorders – a prospective
pilot study. BMC Psychiatry. 24, 401.
mla: Ramming, Hannah, et al. “The Association between Maximal Muscle Strength, Disease
Severity and Psychopharmacotherapy among Young to Middle-Aged Inpatients with
Affective Disorders – a Prospective Pilot Study.” BMC Psychiatry, vol.
24, 401, Springer Nature, 2024, doi:10.1186/s12888-024-05849-2.
short: H. Ramming, L. Theuerkauf, O. Hoos, K. Lichter, S. Kittel-Schneider, BMC
Psychiatry 24 (2024).
date_created: 2024-06-09T22:01:01Z
date_published: 2024-05-29T00:00:00Z
date_updated: 2025-04-23T07:51:51Z
day: '29'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1186/s12888-024-05849-2
external_id:
pmid:
- '38811916'
file:
- access_level: open_access
checksum: 5df60d3c9388955c5b682ea34748d59d
content_type: application/pdf
creator: dernst
date_created: 2024-06-10T10:44:26Z
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file_name: 2024_BMCPsychiatry_Ramming.pdf
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pmid: 1
publication: BMC Psychiatry
publication_identifier:
eissn:
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publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: The association between maximal muscle strength, disease severity and psychopharmacotherapy
among young to middle-aged inpatients with affective disorders – a prospective pilot
study
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: 24
year: '2024'
...
---
OA_place: repository
_id: '18688'
abstract:
- lang: eng
text: The human brain has remarkable computational power. It generates sophisticated
behavioral sequences, stores engrams over an individual’s lifetime, and produces
higher cognitive functions up to the level of consciousness. However, so little
of our neuroscience knowledge covers the human brain, and it remains unknown whether
this organ is truly unique, or is a scaled version of the extensively studied
rodent brain. To address this fundamental question, we determined the cellular,
synaptic, and connectivity rules of the hippocampal CA3 recurrent circuit using
multicellular patch clamp-recording. This circuit is the largest autoassociative
network in the brain, and plays a key role in memory and higher-order computations
such as pattern separation and pattern completion. We demonstrate that human hippocampal
CA3 employs sparse connectivity, in stark contrast to neocortical recurrent networks.
Connectivity sparsifies from rodents to humans, providing a circuit architecture
that maximizes associational power. Unitary synaptic events at human CA3–CA3 synapses
showed both distinct species-specific and circuit-dependent properties, with high
reliability, unique amplitude precision, and long integration times. We also identify
differential scaling rules between hippocampal pathways from rodents to humans,
with a moderate increase in the convergence of CA3 inputs per cell, but a marked
increase in human mossy fiber innervation. Anatomically guided full-scale modeling
suggests that the human brain’s sparse connectivity, expanded neuronal number,
and reliable synaptic signaling combine to enhance the associative memory storage
capacity of CA3. Together, our results reveal unique rules of connectivity and
synaptic signaling in the human hippocampus, demonstrating the absolute necessity
of human brain research and beginning to unravel the remarkable performance of
our autoassociative memory circuits.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: M-Shop
- _id: PreCl
- _id: ScienComp
acknowledgement: We thank Florian Marr for excellent technical assistance, Christina
Altmutter and Julia Flor for technical support, Alois Schlögl for programming, Todor
Asenov for development of the transportation box for human brain tissue, Tim Vogels
for guidance on simulations, Marcus Huber for mathematical advice, and Eleftheria
Kralli-Beller for manuscript editing. This research was supported by the Scientific
Services Units (SSUs) of ISTA, and we are particularly grateful for assistance from
Christoph Sommer and the Imaging and Optics Facility, Preclinical Facility, Life
Science Facility, Miba Machine Shop, and Scientific Computing. We also acknowledge
the excellent support of the Medical University of Vienna Department of Neurosurgery
staff, Romana Hoeftberger and the Division of Neuropathology and Neurochemistry,
and Gregor Kasprian and the Division of Neuroradiology and Musculoskeletal Radiology.
The project received funding from the European Research Council (ERC) under the
European Union’s Horizon 2020 research and innovation programme (Marie Skłodowska-Curie
Actions Individual Fellowship no. 101026635 to J.F.W.), the Austrian Science Fund
(FWF; grant PAT 4178023 to P.J.; grant DK W1232 to M.R.T. and J.G.D.) and the Austrian
Academy of Sciences (DOC fellowship 26137 to M.R.T.).
article_processing_charge: No
author:
- first_name: Jake F.
full_name: Watson, Jake F.
last_name: Watson
- first_name: Victor
full_name: Vargas-Barroso, Victor
last_name: Vargas-Barroso
- first_name: Rebecca J.
full_name: Morse-Mora, Rebecca J.
last_name: Morse-Mora
- first_name: Andrea
full_name: Navas-Olive, Andrea
last_name: Navas-Olive
- first_name: Mojtaba
full_name: Tavakoli, Mojtaba
id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
last_name: Tavakoli
orcid: 0000-0002-7667-6854
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
- first_name: Matthias
full_name: Tomschik, Matthias
last_name: Tomschik
- first_name: Karl
full_name: Rössler, Karl
last_name: Rössler
- 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: Watson JF, Vargas-Barroso V, Morse-Mora RJ, et al. Human hippocampal CA3 uses
specific functional connectivity rules for efficient associative memory. bioRxiv.
doi:10.1101/2024.05.02.592169
apa: Watson, J. F., Vargas-Barroso, V., Morse-Mora, R. J., Navas-Olive, A., Tavakoli,
M., Danzl, J. G., … Jonas, P. M. (n.d.). Human hippocampal CA3 uses specific functional
connectivity rules for efficient associative memory. bioRxiv. https://doi.org/10.1101/2024.05.02.592169
chicago: Watson, Jake F., Victor Vargas-Barroso, Rebecca J. Morse-Mora, Andrea Navas-Olive,
Mojtaba Tavakoli, Johann G Danzl, Matthias Tomschik, Karl Rössler, and Peter M
Jonas. “Human Hippocampal CA3 Uses Specific Functional Connectivity Rules for
Efficient Associative Memory.” BioRxiv, n.d. https://doi.org/10.1101/2024.05.02.592169.
ieee: J. F. Watson et al., “Human hippocampal CA3 uses specific functional
connectivity rules for efficient associative memory,” bioRxiv. .
ista: Watson JF, Vargas-Barroso V, Morse-Mora RJ, Navas-Olive A, Tavakoli M, Danzl
JG, Tomschik M, Rössler K, Jonas PM. Human hippocampal CA3 uses specific functional
connectivity rules for efficient associative memory. bioRxiv, 10.1101/2024.05.02.592169.
mla: Watson, Jake F., et al. “Human Hippocampal CA3 Uses Specific Functional Connectivity
Rules for Efficient Associative Memory.” BioRxiv, doi:10.1101/2024.05.02.592169.
short: J.F. Watson, V. Vargas-Barroso, R.J. Morse-Mora, A. Navas-Olive, M. Tavakoli,
J.G. Danzl, M. Tomschik, K. Rössler, P.M. Jonas, BioRxiv (n.d.).
corr_author: '1'
date_created: 2024-12-19T11:35:08Z
date_published: 2024-05-02T00:00:00Z
date_updated: 2026-04-14T08:34:32Z
day: '02'
department:
- _id: JoDa
- _id: PeJo
doi: 10.1101/2024.05.02.592169
ec_funded: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2024.05.02.592169
month: '05'
oa: 1
oa_version: Preprint
project:
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
- _id: 26AA4EF2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
- _id: 6285a163-2b32-11ec-9570-8e204ca2dba5
grant_number: '26137'
name: Studying Organelle Structure and Function at Nanoscale Resolution with Expansion
Microscopy
publication: bioRxiv
publication_status: draft
related_material:
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relation: dissertation_contains
status: public
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relation: later_version
status: public
status: public
title: Human hippocampal CA3 uses specific functional connectivity rules for efficient
associative memory
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2024'
...
---
OA_place: publisher
OA_type: hybrid
_id: '14257'
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 nanometer synaptic scales in diverse chemically fixed
brain preparations, including rodent and human. CATS uses fixation-compatible
extracellular labeling and optical imaging, including stimulated emission depletion
or expansion microscopy, to comprehensively delineate cellular structures. It
enables three-dimensional reconstruction of single synapses and mapping of synaptic
connectivity by identification and analysis of putative synaptic cleft regions.
Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed
and quantified the synaptic input and output structure of identified neurons.
We furthermore demonstrate applicability to clinically derived human tissue samples,
including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing
the cellular architecture of brain tissue in health and disease.
acknowledged_ssus:
- _id: ScienComp
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: M-Shop
- _id: E-Lib
acknowledgement: 'We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak
for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I.
Erber for technical assistance; and M. Tomschik for support with obtaining human
samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata
for computational support and hardware control. We are grateful to R. Shigemoto
and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University)
for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly
provided by S. Grant (University of Edinburgh). We acknowledge expert support by
Institute of Science and Technology Austria’s scientific computing, imaging and
optics, preclinical and lab support facilities and by the Miba machine shop and
library. We gratefully acknowledge funding by the following sources: Austrian Science
Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232
(J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award
(P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27
(R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.);
European Union’s Horizon 2020 research and innovation programme, European Research
Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020
research and innovation programme, European Research Council (ERC) grant 692692
– GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under
the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions
Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).'
article_processing_charge: Yes (in subscription journal)
article_type: original
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: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- 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: Romana
full_name: Höftberger, Romana
last_name: Höftberger
- 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. Imaging brain tissue architecture
across millimeter to nanometer scales. Nature Biotechnology. 2024;42:1051-1064.
doi:10.1038/s41587-023-01911-8
apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri,
A., … Danzl, J. G. (2024). Imaging brain tissue architecture across millimeter
to nanometer scales. Nature Biotechnology. Springer Nature. https://doi.org/10.1038/s41587-023-01911-8
chicago: Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake
Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture
across Millimeter to Nanometer Scales.” Nature Biotechnology. Springer
Nature, 2024. https://doi.org/10.1038/s41587-023-01911-8.
ieee: J. M. Michalska et al., “Imaging brain tissue architecture across millimeter
to nanometer scales,” Nature Biotechnology, vol. 42. Springer Nature, pp.
1051–1064, 2024.
ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer
CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino
G, Jonas PM, Danzl JG. 2024. Imaging brain tissue architecture across millimeter
to nanometer scales. Nature Biotechnology. 42, 1051–1064.
mla: Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter
to Nanometer Scales.” Nature Biotechnology, vol. 42, Springer Nature, 2024,
pp. 1051–64, doi:10.1038/s41587-023-01911-8.
short: J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri,
C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S.
Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology 42 (2024) 1051–1064.
corr_author: '1'
date_created: 2023-09-03T22:01:15Z
date_published: 2024-07-01T00:00:00Z
date_updated: 2026-04-14T08:34:35Z
day: '01'
ddc:
- '570'
department:
- _id: SaSi
- _id: GaNo
- _id: PeJo
- _id: JoDa
- _id: Bio
- _id: RySh
doi: 10.1038/s41587-023-01911-8
ec_funded: 1
external_id:
isi:
- '001065254200001'
pmid:
- '37653226'
file:
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checksum: 57d5fafb16f02dcb9f7dddb1bd7e2a71
content_type: application/pdf
creator: dernst
date_created: 2025-01-09T07:48:01Z
date_updated: 2025-01-09T07:48:01Z
file_id: '18784'
file_name: 2024_NatureBiotech_Michalska.pdf
file_size: 26065165
relation: main_file
success: 1
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has_accepted_license: '1'
intvolume: ' 42'
isi: 1
language:
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month: '07'
oa: 1
oa_version: Published Version
page: 1051-1064
pmid: 1
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
name: Optical control of synaptic function via adhesion molecules
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232
name: Molecular Drug Targets
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: Synaptic communication in neuronal microcircuits
- _id: 23889792-32DE-11EA-91FC-C7463DDC885E
grant_number: LS18-022
name: High content imaging to decode human immune cell interactions in health and
allergic disease
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _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
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
publication: Nature Biotechnology
publication_identifier:
eissn:
- 1546-1696
issn:
- 1087-0156
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://github.com/danzllab/CATS
record:
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relation: dissertation_contains
status: deleted
- id: '13126'
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relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Imaging brain tissue architecture across millimeter to nanometer scales
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: 42
year: '2024'
...
---
APC_amount: 6248,82 EUR
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '18603'
abstract:
- lang: eng
text: It is widely believed that information storage in neuronal circuits involves
nanoscopic structural changes at synapses, resulting in the formation of synaptic
engrams. However, direct evidence for this hypothesis is lacking. To test this
conjecture, we combined chemical potentiation, functional analysis by paired pre-postsynaptic
recordings, and structural analysis by electron microscopy (EM) and freeze-fracture
replica labeling (FRL) at the rodent hippocampal mossy fiber synapse, a key synapse
in the trisynaptic circuit of the hippocampus. Biophysical analysis of synaptic
transmission revealed that forskolin-induced chemical potentiation increased the
readily releasable vesicle pool size and vesicular release probability by 146%
and 49%, respectively. Structural analysis of mossy fiber synapses by EM and FRL
demonstrated an increase in the number of vesicles close to the plasma membrane
and the number of clusters of the priming protein Munc13-1, indicating an increase
in the number of both docked and primed vesicles. Furthermore, FRL analysis revealed
a significant reduction of the distance between Munc13-1 and CaV2.1 Ca2+ channels,
suggesting reconfiguration of the channel-vesicle coupling nanotopography. Our
results indicate that presynaptic plasticity is associated with structural reorganization
of active zones. We propose that changes in potential nanoscopic organization
at synaptic vesicle release sites may be correlates of learning and memory at
a plastic central synapse.
acknowledged_ssus:
- _id: EM-Fac
- _id: PreCl
acknowledgement: "We thank Carolina Borges-Merjane, Jing-Jing Chen, Katharina Lichter,
and Samuel Young for critically reading the manuscript; the Electron Microscopy
Facility of ISTA, in particular Vanessa Zheden, for extensive support, advice, and
experimental assistance; the Preclinical Facility of ISTA, in particular Victoria
Wimmer and Michael Schunn, for experimental assistance; Florian Marr and Christina
Altmutter for technical support; Alois Schlögl for help with analysis; and Eleftheria
Kralli-Beller for manuscript editing. We also thank Cordelia Imig for providing
Munc13-1cKO-Munc13-2/3(−/−) mutant mice. Part of the work has been published in
O.K.’s thesis in partial fulfillment of the requirements for the degree of Doctor
of Philosophy.\r\nThis project received funding from the European Research Council
and European Union’s Horizon 2020 research and innovation programme (ERC 692692
to P.J.; https://cordis.europa.eu/project/id/692692/de) and from the Fond zur Förderung
der Wissenschaftlichen Forschung (Z312-B27 Wittgenstein award to P.J., https://www.fwf.ac.at/en/funding/portfolio/projects/fwf-wittgenstein-award;
W1205-B09 and P36232-B to P.J., https://www.fwf.ac.at/en/funding; I6166-B to R.S.;
https://www.fwf.ac.at/en/funding). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the manuscript."
article_number: e3002879
article_processing_charge: Yes
article_type: original
author:
- first_name: Olena
full_name: Kim, Olena
id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87
last_name: Kim
orcid: 0000-0003-2344-1039
- first_name: Yuji
full_name: Okamoto, Yuji
id: 3337E116-F248-11E8-B48F-1D18A9856A87
last_name: Okamoto
orcid: 0000-0003-0408-6094
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Nils
full_name: Brose, Nils
last_name: Brose
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- 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, Okamoto Y, Kaufmann W, Brose N, Shigemoto R, Jonas PM. Presynaptic cAMP-PKA-mediated
potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle
coupling at hippocampal mossy fiber boutons. PLoS Biology. 2024;22(11).
doi:10.1371/journal.pbio.3002879
apa: Kim, O., Okamoto, Y., Kaufmann, W., Brose, N., Shigemoto, R., & Jonas,
P. M. (2024). Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration
of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber
boutons. PLoS Biology. Public Library of Science. https://doi.org/10.1371/journal.pbio.3002879
chicago: Kim, Olena, Yuji Okamoto, Walter Kaufmann, Nils Brose, Ryuichi Shigemoto,
and Peter M Jonas. “Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration
of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber
Boutons.” PLoS Biology. Public Library of Science, 2024. https://doi.org/10.1371/journal.pbio.3002879.
ieee: O. Kim, Y. Okamoto, W. Kaufmann, N. Brose, R. Shigemoto, and P. M. Jonas,
“Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic
vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons,”
PLoS Biology, vol. 22, no. 11. Public Library of Science, 2024.
ista: Kim O, Okamoto Y, Kaufmann W, Brose N, Shigemoto R, Jonas PM. 2024. Presynaptic
cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools
and channel-vesicle coupling at hippocampal mossy fiber boutons. PLoS Biology.
22(11), e3002879.
mla: Kim, Olena, et al. “Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration
of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber
Boutons.” PLoS Biology, vol. 22, no. 11, e3002879, Public Library of Science,
2024, doi:10.1371/journal.pbio.3002879.
short: O. Kim, Y. Okamoto, W. Kaufmann, N. Brose, R. Shigemoto, P.M. Jonas, PLoS
Biology 22 (2024).
corr_author: '1'
date_created: 2024-12-01T23:01:54Z
date_published: 2024-11-18T00:00:00Z
date_updated: 2026-04-16T12:20:34Z
day: '18'
ddc:
- '570'
department:
- _id: PeJo
- _id: EM-Fac
- _id: RySh
doi: 10.1371/journal.pbio.3002879
ec_funded: 1
external_id:
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- '001358568700003'
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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
- _id: b1b85715-d554-11ed-a5ad-84a07fc9f18e
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name: Structural & functional basis of presynaptic plasticity
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name: FWF Open Access Fund
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status: public
title: Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic
vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 22
year: '2024'
...
---
_id: '18296'
abstract:
- lang: eng
text: It is widely believed that information storage in neuronal circuits involves
nanoscopic structural changes at synapses, resulting in the formation of synaptic
engrams. However, direct evidence for this hypothesis is lacking. To test this
conjecture, we combined chemical potentiation, functional analysis by paired pre-postsynaptic
recordings, and structural analysis by electron microscopy (EM) and freeze-fracture
replica labeling (FRL) at the murine hippocampal mossy fiber synapse, a key synapse
in the trisynaptic circuit of the hippocampus. Biophysical analysis of synaptic
transmission revealed that forskolin-induced chemical potentiation increased the
readily releasable vesicle pool size and vesicular release probability by 146%
and 49%, respectively. Structural analysis of mossy fiber synapses by EM and FRL
demonstrated an increase in the number of vesicles close to the plasma membrane
and the number of clusters of the priming protein Munc13-1, indicating an increase
in the number of both docked and primed vesicles. Furthermore, FRL analysis revealed
a significant reduction of the distance between Munc13-1 and CaV2.1 Ca2+ channels,
suggesting reconfiguration of the channel-vesicle coupling nanotopography. Our
results indicate that presynaptic plasticity is associated with structural reorganization
of active zones. We propose that changes in potential nanoscopic organization
at synaptic vesicle release sites may be correlates of learning and memory at
a plastic central synapse.
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. Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of
synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber
boutons. 2024. doi:10.15479/AT:ISTA:18296
apa: Kim, O. (2024). Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration
of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber
boutons. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:18296
chicago: Kim, Olena. “Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration
of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber
Boutons.” Institute of Science and Technology Austria, 2024. https://doi.org/10.15479/AT:ISTA:18296.
ieee: O. Kim, “Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration
of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber
boutons.” Institute of Science and Technology Austria, 2024.
ista: Kim O. 2024. Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration
of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber
boutons, Institute of Science and Technology Austria, 10.15479/AT:ISTA:18296.
mla: Kim, Olena. Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration
of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber
Boutons. Institute of Science and Technology Austria, 2024, doi:10.15479/AT:ISTA:18296.
short: O. Kim, (2024).
contributor:
- contributor_type: researcher
first_name: Olena
id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87
last_name: Kim
- contributor_type: researcher
first_name: Yuji
id: 3337E116-F248-11E8-B48F-1D18A9856A87
last_name: Okamoto
orcid: 0000-0003-0408-6094
- contributor_type: researcher
first_name: Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- contributor_type: researcher
first_name: 'Nils '
last_name: Brose
- contributor_type: researcher
first_name: Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- contributor_type: supervisor
first_name: Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
corr_author: '1'
date_created: 2024-10-11T10:12:17Z
date_published: 2024-10-11T00:00:00Z
date_updated: 2026-04-16T12:20:33Z
day: '11'
ddc:
- '570'
department:
- _id: PeJo
- _id: RySh
- _id: EM-Fac
doi: 10.15479/AT:ISTA:18296
ec_funded: 1
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keyword:
- Hippocampal mossy fiber synapses
- short-term potentiation
- long-term potentiation
- presynaptic plasticity
- electron microscopy
- freeze-fracture replica labeling
- paired recordings
- forskolin
- cyclic adenosine monophosphate (cAMP)
- protein kinase A (PKA)
- neuromodulation
- synaptic vesicle pools
- presynaptic Ca2+ channels
- Munc13
- docking
- priming
- active zone
month: '10'
oa: 1
oa_version: Submitted 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
publisher: Institute of Science and Technology Austria
related_material:
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title: Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic
vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons
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: research_data
user_id: 68b8ca59-c5b3-11ee-8790-cd641c68093d
year: '2024'
...
---
OA_place: publisher
OA_type: hybrid
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_id: '14843'
abstract:
- lang: eng
text: The coupling between Ca2+ channels and release sensors is a key factor defining
the signaling properties of a synapse. However, the coupling nanotopography at
many synapses remains unknown, and it is unclear how it changes during development.
To address these questions, we examined coupling at the cerebellar inhibitory
basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission
by paired recording and intracellular pipette perfusion revealed that the effects
of exogenous Ca2+ chelators decreased during development, despite constant reliance
of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica
labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic
P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked
vesicles were only clustered at later developmental stages. Modeling suggested
a developmental transformation from a more random to a more clustered coupling
nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point
configuration, optimizing speed, reliability, and energy efficiency of synaptic
transmission.
acknowledged_ssus:
- _id: EM-Fac
- _id: PreCl
- _id: M-Shop
acknowledgement: We thank Drs. David DiGregorio and Erwin Neher for critically reading
an earlier version of the manuscript, Ralf Schneggenburger for helpful discussions,
Benjamin Suter and Katharina Lichter for support with image analysis, Chris Wojtan
for advice on numerical solution of partial differential equations, Maria Reva for
help with Ripley analysis, Alois Schlögl for programming, and Akari Hagiwara and
Toshihisa Ohtsuka for anti-ELKS antibody. We are grateful to Florian Marr, Christina
Altmutter, and Vanessa Zheden for excellent technical assistance and to Eleftheria
Kralli-Beller for manuscript editing. This research was supported by the Scientific
Services Units (SSUs) of ISTA (Electron Microscopy Facility, Preclinical Facility,
and Machine Shop). The project received funding from the European Research Council
(ERC) under the European Union’s Horizon 2020 research and innovation program (grant
agreement no. 692692), the Fonds zur Förderung der Wissenschaftlichen Forschung
(Z 312-B27, Wittgenstein award; P 36232-B), all to P.J., and a DOC fellowship of
the Austrian Academy of Sciences to J.-J.C.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: JingJing
full_name: Chen, JingJing
id: 2C4E65C8-F248-11E8-B48F-1D18A9856A87
last_name: Chen
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Chong
full_name: Chen, Chong
id: 3DFD581A-F248-11E8-B48F-1D18A9856A87
last_name: Chen
- first_name: Itaru
full_name: Arai, Itaru
id: 32A73F6C-F248-11E8-B48F-1D18A9856A87
last_name: Arai
- first_name: Olena
full_name: Kim, Olena
id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87
last_name: Kim
orcid: 0000-0003-2344-1039
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- 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: Chen J, Kaufmann W, Chen C, et al. Developmental transformation of Ca2+ channel-vesicle
nanotopography at a central GABAergic synapse. Neuron. 2024;112(5):755-771.e9.
doi:10.1016/j.neuron.2023.12.002
apa: Chen, J., Kaufmann, W., Chen, C., Arai, itaru, Kim, O., Shigemoto, R., &
Jonas, P. M. (2024). Developmental transformation of Ca2+ channel-vesicle nanotopography
at a central GABAergic synapse. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2023.12.002
chicago: Chen, JingJing, Walter Kaufmann, Chong Chen, itaru Arai, Olena Kim, Ryuichi
Shigemoto, and Peter M Jonas. “Developmental Transformation of Ca2+ Channel-Vesicle
Nanotopography at a Central GABAergic Synapse.” Neuron. Elsevier, 2024.
https://doi.org/10.1016/j.neuron.2023.12.002.
ieee: J. Chen et al., “Developmental transformation of Ca2+ channel-vesicle
nanotopography at a central GABAergic synapse,” Neuron, vol. 112, no. 5.
Elsevier, p. 755–771.e9, 2024.
ista: Chen J, Kaufmann W, Chen C, Arai itaru, Kim O, Shigemoto R, Jonas PM. 2024.
Developmental transformation of Ca2+ channel-vesicle nanotopography at a central
GABAergic synapse. Neuron. 112(5), 755–771.e9.
mla: Chen, JingJing, et al. “Developmental Transformation of Ca2+ Channel-Vesicle
Nanotopography at a Central GABAergic Synapse.” Neuron, vol. 112, no. 5,
Elsevier, 2024, p. 755–771.e9, doi:10.1016/j.neuron.2023.12.002.
short: J. Chen, W. Kaufmann, C. Chen, itaru Arai, O. Kim, R. Shigemoto, P.M. Jonas,
Neuron 112 (2024) 755–771.e9.
corr_author: '1'
date_created: 2024-01-21T23:00:56Z
date_published: 2024-03-06T00:00:00Z
date_updated: 2026-05-18T22:30:27Z
day: '06'
ddc:
- '570'
department:
- _id: PeJo
- _id: EM-Fac
- _id: RySh
doi: 10.1016/j.neuron.2023.12.002
ec_funded: 1
external_id:
isi:
- '001202925700001'
pmid:
- '38215739'
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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
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grant_number: P36232
name: Mechanisms of GABA release in hippocampal circuits
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grant_number: '25383'
name: Development of nanodomain coupling between Ca2+ channels and release sensors
at a central inhibitory synapse
publication: Neuron
publication_identifier:
eissn:
- 1097-4199
issn:
- 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on ISTA Website
relation: press_release
url: https://ista.ac.at/en/news/synapses-brought-to-the-point/
record:
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status: public
scopus_import: '1'
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title: Developmental transformation of Ca2+ channel-vesicle nanotopography at a central
GABAergic 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: 112
year: '2024'
...
---
OA_place: publisher
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abstract:
- lang: eng
text: "The coupling between presynaptic Ca2+ channels and release sensors is a key
factor that\r\ndetermines speed and efficacy of synapse transmission. At some
excitatory synapses,\r\nchannel–sensor coupling becomes tighter during development,
and tightening is often\r\nassociated with a switch in the reliance on different
Ca2+ channel subtypes. However, the\r\ncoupling topography at many synapses remains
unknown, and it is unclear how it changes\r\nduring development. To address this
question, we analyzed the coupling configuration at the\r\ncerebellar basket cell
(BC) to Purkinje cell (PC) synapse at different developmental stages,\r\ncombining
biophysical analysis, structural analysis, and modeling.\r\nQuantal analysis of
BC–PC indicated that release probability decreased, while the\r\nnumber of functional
sites increased during development. Although transmitter release\r\npersistently
relied on P/Q-type Ca2+ channels in the time period postnatal day 7–23, effects\r\nof
the Ca2+ chelator EGTA and BAPTA applied by intracellular pipette perfusion decreased\r\nduring
development, indicative of tightening of source-sensor coupling. Furthermore,\r\npresynaptic
action potentials became shorter during development, suggesting reduced\r\nefficacy
of Ca2+ channel activation.\r\nStructural analysis by freeze-fracture replica
labeling (FRL) and transmission electron\r\nmicroscopy (EM) indicated that presynaptic
P/Q-type Ca2+ channels formed nanoclusters\r\nthroughout development, whereas
docked vesicles were only clustered at later\r\ndevelopmental stages. The number
of functional release sites correlated better with the AZ\r\nnumber early in development,
but match better with the Ca2+ channel cluster number at later\r\nstages.\r\nModeling
suggested a developmental transformation from a more random to a more\r\nclustered
coupling nanotopography. Thus, presynaptic signaling developmentally approaches\r\na
point-to-point configuration, optimizing speed, reliability, and energy efficiency
of synaptic\r\ntransmission."
acknowledged_ssus:
- _id: EM-Fac
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: JingJing
full_name: Chen, JingJing
id: 2C4E65C8-F248-11E8-B48F-1D18A9856A87
last_name: Chen
citation:
ama: Chen J. Developmental transformation of nanodomain coupling between Ca2+ channels
and release sensors at a central GABAergic synapse. 2024. doi:10.15479/at:ista:15101
apa: Chen, J. (2024). Developmental transformation of nanodomain coupling between
Ca2+ channels and release sensors at a central GABAergic synapse. Institute
of Science and Technology Austria. https://doi.org/10.15479/at:ista:15101
chicago: Chen, JingJing. “Developmental Transformation of Nanodomain Coupling between
Ca2+ Channels and Release Sensors at a Central GABAergic Synapse.” Institute of
Science and Technology Austria, 2024. https://doi.org/10.15479/at:ista:15101.
ieee: J. Chen, “Developmental transformation of nanodomain coupling between Ca2+
channels and release sensors at a central GABAergic synapse,” Institute of Science
and Technology Austria, 2024.
ista: Chen J. 2024. Developmental transformation of nanodomain coupling between
Ca2+ channels and release sensors at a central GABAergic synapse. Institute of
Science and Technology Austria.
mla: Chen, JingJing. Developmental Transformation of Nanodomain Coupling between
Ca2+ Channels and Release Sensors at a Central GABAergic Synapse. Institute
of Science and Technology Austria, 2024, doi:10.15479/at:ista:15101.
short: J. Chen, Developmental Transformation of Nanodomain Coupling between Ca2+
Channels and Release Sensors at a Central GABAergic Synapse, Institute of Science
and Technology Austria, 2024.
corr_author: '1'
date_created: 2024-03-11T10:09:54Z
date_published: 2024-03-11T00:00:00Z
date_updated: 2026-04-07T13:24:22Z
day: '11'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: PeJo
doi: 10.15479/at:ista:15101
ec_funded: 1
file:
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checksum: db4947474ffa271e66c254b6fe876a55
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: jchen
date_created: 2024-03-11T14:10:58Z
date_updated: 2024-04-02T22:30:03Z
embargo_to: open_access
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file_name: Thesis_Jingjing CHEN.docx
file_size: 11271363
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checksum: a5eeae8b5702cd540f5d03469bc33dde
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creator: jchen
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file_size: 16627311
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file_date_updated: 2024-04-02T22:30:03Z
has_accepted_license: '1'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: '84'
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
- _id: 26B66A3E-B435-11E9-9278-68D0E5697425
grant_number: '25383'
name: Development of nanodomain coupling between Ca2+ channels and release sensors
at a central inhibitory synapse
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '14843'
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: Developmental transformation of nanodomain coupling between Ca2+ channels and
release sensors at a central GABAergic 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: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
APC_amount: 5887,8 EUR
OA_place: publisher
OA_type: hybrid
_id: '15084'
abstract:
- lang: eng
text: "GABAB receptor (GBR) activation inhibits neurotransmitter release in axon
terminals in the brain, except in medial habenula (MHb) terminals, which show
robust potentiation. However, mechanisms underlying this enigmatic potentiation
remain elusive. Here, we report that GBR activation on MHb terminals induces an
activity-dependent transition from a facilitating, tonic to a depressing, phasic
neurotransmitter release mode. This transition is accompanied by a 4.1-fold increase
in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked
synaptic vesicles (SVs) at the presynaptic active zone (AZ). Strikingly, the depressing
phasic release exhibits looser coupling distance than the tonic release. Furthermore,
the tonic and phasic release are selectively affected by deletion of synaptoporin
(SPO) and Ca\r\n 2+\r\n -dependent
activator protein for secretion 2 (CAPS2), respectively. SPO modulates augmentation,
the short-term plasticity associated with tonic release, and CAPS2 retains the
increased RRP for initial responses in phasic response trains. The cytosolic protein
CAPS2 showed a SV-associated distribution similar to the vesicular transmembrane
protein SPO, and they were colocalized in the same terminals. We developed the
“Flash and Freeze-fracture” method, and revealed the release of SPO-associated
vesicles in both tonic and phasic modes and activity-dependent recruitment of
CAPS2 to the AZ during phasic release, which lasted several minutes. Overall,
these results indicate that GBR activation translocates CAPS2 to the AZ along
with the fusion of CAPS2-associated SVs, contributing to persistency of the RRP
increase. Thus, we identified structural and molecular mechanisms underlying tonic
and phasic neurotransmitter release and their transition by GBR activation in
MHb terminals."
acknowledged_ssus:
- _id: M-Shop
- _id: PreCl
- _id: EM-Fac
acknowledgement: We thank Erwin Neher and Ipe Ninan for critical comments on the manuscript.
This project has received funding from the European Research Council (ERC) and European
Commission, under the European Union’s Horizon 2020 research and innovation program
(ERC grant agreement no. 694539 to R.S. and the Marie Skłodowska-Curie grant agreement
no. 665385 to C.Ö.). This study was supported by the Cooperative Study Program of
Center for Animal Resources and Collaborative Study of NINS. We thank Kohgaku Eguchi
for statistical analysis, Yu Kasugai for additional EM imaging, Robert Beattie for
the design of the slice recovery chamber for Flash and Freeze experiments, Todor
Asenov from the ISTA machine shop for custom part preparations for high-pressure
freezing, the ISTA preclinical facility for animal caretaking, and the ISTA EM facilities
for technical support.
article_number: e2301449121
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Peter
full_name: Koppensteiner, Peter
id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
last_name: Koppensteiner
orcid: 0000-0002-3509-1948
- first_name: Pradeep
full_name: Bhandari, Pradeep
id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87
last_name: Bhandari
orcid: 0000-0003-0863-4481
- 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: Carolina
full_name: Borges Merjane, Carolina
id: 4305C450-F248-11E8-B48F-1D18A9856A87
last_name: Borges Merjane
orcid: 0000-0003-0005-401X
- first_name: Elodie
full_name: Le Monnier, Elodie
id: 3B59276A-F248-11E8-B48F-1D18A9856A87
last_name: Le Monnier
- first_name: Utsa
full_name: Roy, Utsa
id: 4d26cf11-5355-11ee-ae5a-eb05e255b9b2
last_name: Roy
- first_name: Yukihiro
full_name: Nakamura, Yukihiro
last_name: Nakamura
- first_name: Tetsushi
full_name: Sadakata, Tetsushi
last_name: Sadakata
- first_name: Makoto
full_name: Sanbo, Makoto
last_name: Sanbo
- first_name: Masumi
full_name: Hirabayashi, Masumi
last_name: Hirabayashi
- first_name: JeongSeop
full_name: Rhee, JeongSeop
last_name: Rhee
- first_name: Nils
full_name: Brose, Nils
last_name: Brose
- 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: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
citation:
ama: Koppensteiner P, Bhandari P, Önal C, et al. GABAB receptors induce phasic release
from medial habenula terminals through activity-dependent recruitment of release-ready
vesicles. Proceedings of the National Academy of Sciences of the United States
of America. 2024;121(8). doi:10.1073/pnas.2301449121
apa: Koppensteiner, P., Bhandari, P., Önal, C., Borges Merjane, C., Le Monnier,
E., Roy, U., … Shigemoto, R. (2024). GABAB receptors induce phasic release from
medial habenula terminals through activity-dependent recruitment of release-ready
vesicles. Proceedings of the National Academy of Sciences of the United States
of America. National Academy of Sciences. https://doi.org/10.1073/pnas.2301449121
chicago: Koppensteiner, Peter, Pradeep Bhandari, Cihan Önal, Carolina Borges Merjane,
Elodie Le Monnier, Utsa Roy, Yukihiro Nakamura, et al. “GABAB Receptors Induce
Phasic Release from Medial Habenula Terminals through Activity-Dependent Recruitment
of Release-Ready Vesicles.” Proceedings of the National Academy of Sciences
of the United States of America. National Academy of Sciences, 2024. https://doi.org/10.1073/pnas.2301449121.
ieee: P. Koppensteiner et al., “GABAB receptors induce phasic release from
medial habenula terminals through activity-dependent recruitment of release-ready
vesicles,” Proceedings of the National Academy of Sciences of the United States
of America, vol. 121, no. 8. National Academy of Sciences, 2024.
ista: Koppensteiner P, Bhandari P, Önal C, Borges Merjane C, Le Monnier E, Roy U,
Nakamura Y, Sadakata T, Sanbo M, Hirabayashi M, Rhee J, Brose N, Jonas PM, Shigemoto
R. 2024. GABAB receptors induce phasic release from medial habenula terminals
through activity-dependent recruitment of release-ready vesicles. Proceedings
of the National Academy of Sciences of the United States of America. 121(8), e2301449121.
mla: Koppensteiner, Peter, et al. “GABAB Receptors Induce Phasic Release from Medial
Habenula Terminals through Activity-Dependent Recruitment of Release-Ready Vesicles.”
Proceedings of the National Academy of Sciences of the United States of America,
vol. 121, no. 8, e2301449121, National Academy of Sciences, 2024, doi:10.1073/pnas.2301449121.
short: P. Koppensteiner, P. Bhandari, C. Önal, C. Borges Merjane, E. Le Monnier,
U. Roy, Y. Nakamura, T. Sadakata, M. Sanbo, M. Hirabayashi, J. Rhee, N. Brose,
P.M. Jonas, R. Shigemoto, Proceedings of the National Academy of Sciences of the
United States of America 121 (2024).
corr_author: '1'
date_created: 2024-03-05T09:23:55Z
date_published: 2024-02-20T00:00:00Z
date_updated: 2026-05-18T22:30:29Z
day: '20'
ddc:
- '570'
department:
- _id: RySh
- _id: PeJo
doi: 10.1073/pnas.2301449121
ec_funded: 1
external_id:
isi:
- '001208567300006'
pmid:
- '38346189'
file:
- access_level: open_access
checksum: b25b2a057c266ff317a48b0d54d6fc8a
content_type: application/pdf
creator: dernst
date_created: 2024-03-12T13:42:42Z
date_updated: 2024-03-12T13:42:42Z
file_id: '15110'
file_name: 2024_PNAS_Koppensteiner.pdf
file_size: 13648221
relation: main_file
success: 1
file_date_updated: 2024-03-12T13:42:42Z
has_accepted_license: '1'
intvolume: ' 121'
isi: 1
issue: '8'
language:
- iso: eng
month: '02'
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: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication: Proceedings of the National Academy of Sciences of the United States
of America
publication_identifier:
eissn:
- 1091-6490
issn:
- 0027-8424
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
link:
- description: News on ISTA Website
relation: press_release
url: https://ista.ac.at/en/news/neuronal-insights-flash-and-freeze-fracture/
record:
- id: '13173'
relation: research_data
status: public
- id: '19271'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: GABAB receptors induce phasic release from medial habenula terminals through
activity-dependent recruitment of release-ready vesicles
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: 121
year: '2024'
...
---
_id: '12515'
abstract:
- lang: eng
text: "Introduction: The olfactory system in most mammals is divided into several
subsystems based on the anatomical locations of the neuroreceptor cells involved
and the receptor families that are expressed. In addition to the main olfactory
system and the vomeronasal system, a range of olfactory subsystems converge onto
the transition zone located between the main olfactory bulb (MOB) and the accessory
olfactory bulb (AOB), which has been termed the olfactory limbus (OL). The OL
contains specialized glomeruli that receive noncanonical sensory afferences and
which interact with the MOB and AOB. Little is known regarding the olfactory subsystems
of mammals other than laboratory rodents.\r\nMethods: We have focused on characterizing
the OL in the red fox by performing general and specific histological stainings
on serial sections, using both single and double immunohistochemical and lectin-histochemical
labeling techniques.\r\nResults: As a result, we have been able to determine that
the OL of the red fox (Vulpes vulpes) displays an uncommonly high degree of development
and complexity.\r\nDiscussion: This makes this species a novel mammalian model,
the study of which could improve our understanding of the noncanonical pathways
involved in the processing of chemosensory cues."
acknowledgement: This work was partially supported by a grant from “Consello Social
Universidade de Santiago de Compostela” 2022-PU004.We would like to show special
gratitude to Prof. Ludwig Wagner (Medical University, Vienna) for kindly providing
us with the secretagogin antibody. We thank the Wildlife Recovery Centres of Galicia,
Dirección Xeral de Patrimonio Natural (Xunta de Galicia, Spain), and Federación
Galega de Caza for providing the red foxes used in this study.
article_number: '1097467'
article_processing_charge: No
article_type: original
author:
- first_name: Irene
full_name: Ortiz-Leal, Irene
last_name: Ortiz-Leal
- first_name: Mateo V.
full_name: Torres, Mateo V.
last_name: Torres
- first_name: Victor M
full_name: Vargas Barroso, Victor M
id: 2F55A9DE-F248-11E8-B48F-1D18A9856A87
last_name: Vargas Barroso
- first_name: Luis Eusebio
full_name: Fidalgo, Luis Eusebio
last_name: Fidalgo
- first_name: Ana María
full_name: López-Beceiro, Ana María
last_name: López-Beceiro
- first_name: Jorge A.
full_name: Larriva-Sahd, Jorge A.
last_name: Larriva-Sahd
- first_name: Pablo
full_name: Sánchez-Quinteiro, Pablo
last_name: Sánchez-Quinteiro
citation:
ama: Ortiz-Leal I, Torres MV, Vargas Barroso VM, et al. The olfactory limbus of
the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb
pathway. Frontiers in Neuroanatomy. 2023;16. doi:10.3389/fnana.2022.1097467
apa: Ortiz-Leal, I., Torres, M. V., Vargas Barroso, V. M., Fidalgo, L. E., López-Beceiro,
A. M., Larriva-Sahd, J. A., & Sánchez-Quinteiro, P. (2023). The olfactory
limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory
bulb pathway. Frontiers in Neuroanatomy. Frontiers. https://doi.org/10.3389/fnana.2022.1097467
chicago: Ortiz-Leal, Irene, Mateo V. Torres, Victor M Vargas Barroso, Luis Eusebio
Fidalgo, Ana María López-Beceiro, Jorge A. Larriva-Sahd, and Pablo Sánchez-Quinteiro.
“The Olfactory Limbus of the Red Fox (Vulpes Vulpes). New Insights Regarding a
Noncanonical Olfactory Bulb Pathway.” Frontiers in Neuroanatomy. Frontiers,
2023. https://doi.org/10.3389/fnana.2022.1097467.
ieee: I. Ortiz-Leal et al., “The olfactory limbus of the red fox (Vulpes
vulpes). New insights regarding a noncanonical olfactory bulb pathway,” Frontiers
in Neuroanatomy, vol. 16. Frontiers, 2023.
ista: Ortiz-Leal I, Torres MV, Vargas Barroso VM, Fidalgo LE, López-Beceiro AM,
Larriva-Sahd JA, Sánchez-Quinteiro P. 2023. The olfactory limbus of the red fox
(Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway.
Frontiers in Neuroanatomy. 16, 1097467.
mla: Ortiz-Leal, Irene, et al. “The Olfactory Limbus of the Red Fox (Vulpes Vulpes).
New Insights Regarding a Noncanonical Olfactory Bulb Pathway.” Frontiers in
Neuroanatomy, vol. 16, 1097467, Frontiers, 2023, doi:10.3389/fnana.2022.1097467.
short: I. Ortiz-Leal, M.V. Torres, V.M. Vargas Barroso, L.E. Fidalgo, A.M. López-Beceiro,
J.A. Larriva-Sahd, P. Sánchez-Quinteiro, Frontiers in Neuroanatomy 16 (2023).
date_created: 2023-02-05T23:01:00Z
date_published: 2023-01-10T00:00:00Z
date_updated: 2023-08-16T11:37:52Z
day: '10'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.3389/fnana.2022.1097467
external_id:
isi:
- '000919786900001'
pmid:
- '36704406'
file:
- access_level: open_access
checksum: 49cd40f3bda6f267079427042e7d15e3
content_type: application/pdf
creator: dernst
date_created: 2023-02-06T07:56:14Z
date_updated: 2023-02-06T07:56:14Z
file_id: '12518'
file_name: 2022_FrontiersNeuroanatomy_OrtizLeal.pdf
file_size: 21943473
relation: main_file
success: 1
file_date_updated: 2023-02-06T07:56:14Z
has_accepted_license: '1'
intvolume: ' 16'
isi: 1
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
pmid: 1
publication: Frontiers in Neuroanatomy
publication_identifier:
eissn:
- 1662-5129
publication_status: published
publisher: Frontiers
quality_controlled: '1'
scopus_import: '1'
status: public
title: The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding
a noncanonical olfactory bulb pathway
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: 16
year: '2023'
...
---
_id: '12567'
abstract:
- lang: eng
text: Single-molecule localization microscopy (SMLM) greatly advances structural
studies of diverse biological tissues. For example, presynaptic active zone (AZ)
nanotopology is resolved in increasing detail. Immunofluorescence imaging of AZ
proteins usually relies on epitope preservation using aldehyde-based immunocompetent
fixation. Cryofixation techniques, such as high-pressure freezing (HPF) and freeze
substitution (FS), are widely used for ultrastructural studies of presynaptic
architecture in electron microscopy (EM). HPF/FS demonstrated nearer-to-native
preservation of AZ ultrastructure, e.g., by facilitating single filamentous structures.
Here, we present a protocol combining the advantages of HPF/FS and direct stochastic
optical reconstruction microscopy (dSTORM) to quantify nanotopology of the AZ
scaffold protein Bruchpilot (Brp) at neuromuscular junctions (NMJs) of Drosophila
melanogaster. Using this standardized model, we tested for preservation of Brp
clusters in different FS protocols compared to classical aldehyde fixation. In
HPF/FS samples, presynaptic boutons were structurally well preserved with ~22%
smaller Brp clusters that allowed quantification of subcluster topology. In summary,
we established a standardized near-to-native preparation and immunohistochemistry
protocol for SMLM analyses of AZ protein clusters in a defined model synapse.
Our protocol could be adapted to study protein arrangements at single-molecule
resolution in other intact tissue preparations.
acknowledgement: This work has been supported by funding of the German Research Foundation
(Deutsche Forschungsgemeinschaft [DFG], CRC 166, Project B06 to M.H. and A.-L.S.,
FOR 3004 SYNABS P1 to M.H.) and by the Interdisciplinary Clinical Research Center
(IZKF) Würzburg (Z-3/69 to M.M.P., N-229 to M.H. and A.-L.S.). A.M. is funded by
the University of Leipzig Clinician Scientist Program.
article_number: '2128'
article_processing_charge: No
article_type: original
author:
- first_name: Achmed
full_name: Mrestani, Achmed
last_name: Mrestani
- first_name: Katharina
full_name: Lichter, Katharina
id: 39302e62-fcfc-11ec-8196-8b01447dbd3d
last_name: Lichter
orcid: 0000-0002-1485-0351
- first_name: Anna Leena
full_name: Sirén, Anna Leena
last_name: Sirén
- first_name: Manfred
full_name: Heckmann, Manfred
last_name: Heckmann
- first_name: Mila M.
full_name: Paul, Mila M.
last_name: Paul
- first_name: Martin
full_name: Pauli, Martin
last_name: Pauli
citation:
ama: Mrestani A, Lichter K, Sirén AL, Heckmann M, Paul MM, Pauli M. Single-molecule
localization microscopy of presynaptic active zones in Drosophila melanogaster
after rapid cryofixation. International Journal of Molecular Sciences.
2023;24(3). doi:10.3390/ijms24032128
apa: Mrestani, A., Lichter, K., Sirén, A. L., Heckmann, M., Paul, M. M., & Pauli,
M. (2023). Single-molecule localization microscopy of presynaptic active zones
in Drosophila melanogaster after rapid cryofixation. International Journal
of Molecular Sciences. MDPI. https://doi.org/10.3390/ijms24032128
chicago: Mrestani, Achmed, Katharina Lichter, Anna Leena Sirén, Manfred Heckmann,
Mila M. Paul, and Martin Pauli. “Single-Molecule Localization Microscopy of Presynaptic
Active Zones in Drosophila Melanogaster after Rapid Cryofixation.” International
Journal of Molecular Sciences. MDPI, 2023. https://doi.org/10.3390/ijms24032128.
ieee: A. Mrestani, K. Lichter, A. L. Sirén, M. Heckmann, M. M. Paul, and M. Pauli,
“Single-molecule localization microscopy of presynaptic active zones in Drosophila
melanogaster after rapid cryofixation,” International Journal of Molecular
Sciences, vol. 24, no. 3. MDPI, 2023.
ista: Mrestani A, Lichter K, Sirén AL, Heckmann M, Paul MM, Pauli M. 2023. Single-molecule
localization microscopy of presynaptic active zones in Drosophila melanogaster
after rapid cryofixation. International Journal of Molecular Sciences. 24(3),
2128.
mla: Mrestani, Achmed, et al. “Single-Molecule Localization Microscopy of Presynaptic
Active Zones in Drosophila Melanogaster after Rapid Cryofixation.” International
Journal of Molecular Sciences, vol. 24, no. 3, 2128, MDPI, 2023, doi:10.3390/ijms24032128.
short: A. Mrestani, K. Lichter, A.L. Sirén, M. Heckmann, M.M. Paul, M. Pauli, International
Journal of Molecular Sciences 24 (2023).
date_created: 2023-02-19T23:00:56Z
date_published: 2023-01-21T00:00:00Z
date_updated: 2025-04-23T08:48:27Z
day: '21'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.3390/ijms24032128
external_id:
isi:
- '000930324700001'
pmid:
- '36768451'
file:
- access_level: open_access
checksum: 69a35dcd3e0249f902ab881b06ee2e58
content_type: application/pdf
creator: dernst
date_created: 2023-02-20T07:09:27Z
date_updated: 2023-02-20T07:09:27Z
file_id: '12569'
file_name: 2023_IJMS_Mrestani.pdf
file_size: 2823025
relation: main_file
success: 1
file_date_updated: 2023-02-20T07:09:27Z
has_accepted_license: '1'
intvolume: ' 24'
isi: 1
issue: '3'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
pmid: 1
publication: International Journal of Molecular Sciences
publication_identifier:
eissn:
- 1422-0067
publication_status: published
publisher: MDPI
quality_controlled: '1'
scopus_import: '1'
status: public
title: Single-molecule localization microscopy of presynaptic active zones in Drosophila
melanogaster after rapid cryofixation
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: 24
year: '2023'
...
---
OA_place: repository
OA_type: green
_id: '12720'
abstract:
- lang: eng
text: Here we describe the in vivo DNA assembly approach, where molecular cloning
procedures are performed using an E. coli recA-independent recombination pathway,
which assembles linear fragments of DNA with short homologous termini. This pathway
is present in all standard laboratory E. coli strains and, by bypassing the need
for in vitro DNA assembly, allows simplified molecular cloning to be performed
without the plasmid instability issues associated with specialized recombination-cloning
bacterial strains. The methodology requires specific primer design and can perform
all standard plasmid modifications (insertions, deletions, mutagenesis, and sub-cloning)
in a rapid, simple, and cost-efficient manner, as it does not require commercial
kits or specialized bacterial strains. Additionally, this approach can be used
to perform complex procedures such as multiple modifications to a plasmid, as
up to 6 linear fragments can be assembled in vivo by this recombination pathway.
Procedures generally require less than 3 h, involving PCR amplification, DpnI
digestion of template DNA, and transformation, upon which circular plasmids are
assembled. In this chapter we describe the requirements, procedure, and potential
pitfalls when using this technique, as well as protocol variations to overcome
the most common issues.
alternative_title:
- Methods in Molecular Biology
article_processing_charge: No
author:
- first_name: Sandra
full_name: Arroyo-Urea, Sandra
last_name: Arroyo-Urea
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Javier
full_name: García-Nafría, Javier
last_name: García-Nafría
citation:
ama: 'Arroyo-Urea S, Watson J, García-Nafría J. Molecular Cloning Using In Vivo
DNA Assembly. In: Scarlett G, ed. DNA Manipulation and Analysis. Vol 2633.
MIMB. New York, NY, United States: Springer Nature; 2023:33-44. doi:10.1007/978-1-0716-3004-4_3'
apa: 'Arroyo-Urea, S., Watson, J., & García-Nafría, J. (2023). Molecular Cloning
Using In Vivo DNA Assembly. In G. Scarlett (Ed.), DNA Manipulation and Analysis
(Vol. 2633, pp. 33–44). New York, NY, United States: Springer Nature. https://doi.org/10.1007/978-1-0716-3004-4_3'
chicago: 'Arroyo-Urea, Sandra, Jake Watson, and Javier García-Nafría. “Molecular
Cloning Using In Vivo DNA Assembly.” In DNA Manipulation and Analysis,
edited by Garry Scarlett, 2633:33–44. MIMB. New York, NY, United States: Springer
Nature, 2023. https://doi.org/10.1007/978-1-0716-3004-4_3.'
ieee: 'S. Arroyo-Urea, J. Watson, and J. García-Nafría, “Molecular Cloning Using
In Vivo DNA Assembly,” in DNA Manipulation and Analysis, vol. 2633, G.
Scarlett, Ed. New York, NY, United States: Springer Nature, 2023, pp. 33–44.'
ista: 'Arroyo-Urea S, Watson J, García-Nafría J. 2023.Molecular Cloning Using In
Vivo DNA Assembly. In: DNA Manipulation and Analysis. Methods in Molecular Biology,
vol. 2633, 33–44.'
mla: Arroyo-Urea, Sandra, et al. “Molecular Cloning Using In Vivo DNA Assembly.”
DNA Manipulation and Analysis, edited by Garry Scarlett, vol. 2633, Springer
Nature, 2023, pp. 33–44, doi:10.1007/978-1-0716-3004-4_3.
short: S. Arroyo-Urea, J. Watson, J. García-Nafría, in:, G. Scarlett (Ed.), DNA
Manipulation and Analysis, Springer Nature, New York, NY, United States, 2023,
pp. 33–44.
date_created: 2023-03-12T23:01:02Z
date_published: 2023-03-01T00:00:00Z
date_updated: 2025-06-25T05:56:45Z
day: '01'
department:
- _id: PeJo
doi: 10.1007/978-1-0716-3004-4_3
editor:
- first_name: Garry
full_name: Scarlett, Garry
last_name: Scarlett
external_id:
pmid:
- '36853454'
intvolume: ' 2633'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://zaguan.unizar.es/record/125930/files/texto_completo.pdf
month: '03'
oa: 1
oa_version: Submitted Version
page: 33-44
place: New York, NY, United States
pmid: 1
publication: DNA Manipulation and Analysis
publication_identifier:
eisbn:
- 978-1-0716-3004-4
eissn:
- 1940-6029
isbn:
- 978-1-0716-3003-7
issn:
- 1064-3745
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
series_title: MIMB
status: public
title: Molecular Cloning Using In Vivo DNA Assembly
type: book_chapter
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 2633
year: '2023'
...