---
_id: '1323'
abstract:
- lang: eng
  text: Mossy fiber synapses on CA3 pyramidal cells are 'conditional detonators' that
    reliably discharge postsynaptic targets. The 'conditional' nature implies that
    burst activity in dentate gyrus granule cells is required for detonation. Whether
    single unitary excitatory postsynaptic potentials (EPSPs) trigger spikes in CA3
    neurons remains unknown. Mossy fiber synapses exhibit both pronounced short-term
    facilitation and uniquely large post-tetanic potentiation (PTP). We tested whether
    PTP could convert mossy fiber synapses from subdetonator into detonator mode,
    using a recently developed method to selectively and noninvasively stimulate individual
    presynaptic terminals in rat brain slices. Unitary EPSPs failed to initiate a
    spike in CA3 neurons under control conditions, but reliably discharged them after
    induction of presynaptic short-term plasticity. Remarkably, PTP switched mossy
    fiber synapses into full detonators for tens of seconds. Plasticity-dependent
    detonation may be critical for efficient coding, storage, and recall of information
    in the granule cell–CA3 cell network.
acknowledged_ssus:
- _id: M-Shop
- _id: PreCl
article_number: e17977
author:
- first_name: Nicholas
  full_name: Vyleta, Nicholas
  id: 36C4978E-F248-11E8-B48F-1D18A9856A87
  last_name: Vyleta
- first_name: Carolina
  full_name: Borges Merjane, Carolina
  id: 4305C450-F248-11E8-B48F-1D18A9856A87
  last_name: Borges Merjane
  orcid: 0000-0003-0005-401X
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
citation:
  ama: Vyleta N, Borges Merjane C, Jonas PM. Plasticity-dependent, full detonation
    at hippocampal mossy fiber–CA3 pyramidal neuron synapses. <i>eLife</i>. 2016;5.
    doi:<a href="https://doi.org/10.7554/eLife.17977">10.7554/eLife.17977</a>
  apa: Vyleta, N., Borges Merjane, C., &#38; Jonas, P. M. (2016). Plasticity-dependent,
    full detonation at hippocampal mossy fiber–CA3 pyramidal neuron synapses. <i>ELife</i>.
    eLife Sciences Publications. <a href="https://doi.org/10.7554/eLife.17977">https://doi.org/10.7554/eLife.17977</a>
  chicago: Vyleta, Nicholas, Carolina Borges Merjane, and Peter M Jonas. “Plasticity-Dependent,
    Full Detonation at Hippocampal Mossy Fiber–CA3 Pyramidal Neuron Synapses.” <i>ELife</i>.
    eLife Sciences Publications, 2016. <a href="https://doi.org/10.7554/eLife.17977">https://doi.org/10.7554/eLife.17977</a>.
  ieee: N. Vyleta, C. Borges Merjane, and P. M. Jonas, “Plasticity-dependent, full
    detonation at hippocampal mossy fiber–CA3 pyramidal neuron synapses,” <i>eLife</i>,
    vol. 5. eLife Sciences Publications, 2016.
  ista: Vyleta N, Borges Merjane C, Jonas PM. 2016. Plasticity-dependent, full detonation
    at hippocampal mossy fiber–CA3 pyramidal neuron synapses. eLife. 5, e17977.
  mla: Vyleta, Nicholas, et al. “Plasticity-Dependent, Full Detonation at Hippocampal
    Mossy Fiber–CA3 Pyramidal Neuron Synapses.” <i>ELife</i>, vol. 5, e17977, eLife
    Sciences Publications, 2016, doi:<a href="https://doi.org/10.7554/eLife.17977">10.7554/eLife.17977</a>.
  short: N. Vyleta, C. Borges Merjane, P.M. Jonas, ELife 5 (2016).
date_created: 2018-12-11T11:51:22Z
date_published: 2016-10-25T00:00:00Z
date_updated: 2023-02-21T10:34:24Z
day: '25'
ddc:
- '571'
- '572'
department:
- _id: PeJo
doi: 10.7554/eLife.17977
ec_funded: 1
file:
- access_level: open_access
  checksum: a7201280c571bed88ebd459ce5ce6a47
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:17:05Z
  date_updated: 2020-07-14T12:44:44Z
  file_id: '5257'
  file_name: IST-2016-715-v1+1_e17977-download.pdf
  file_size: 1477891
  relation: main_file
file_date_updated: 2020-07-14T12:44:44Z
has_accepted_license: '1'
intvolume: '         5'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
project:
- _id: 25C0F108-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '268548'
  name: Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glumatergic synapse
publication: eLife
publication_status: published
publisher: eLife Sciences Publications
publist_id: '5947'
pubrep_id: '715'
quality_controlled: '1'
scopus_import: 1
status: public
title: Plasticity-dependent, full detonation at hippocampal mossy fiber–CA3 pyramidal
  neuron synapses
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 5
year: '2016'
...
---
_id: '2229'
abstract:
- lang: eng
  text: The distance between Ca^2+ channels and release sensors determines the speed
    and efficacy of synaptic transmission. Tight &quot;nanodomain&quot; channel-sensor
    coupling initiates transmitter release at synapses in the mature brain, whereas
    loose &quot;microdomain&quot; coupling appears restricted to early developmental
    stages. To probe the coupling configuration at a plastic synapse in the mature
    central nervous system, we performed paired recordings between mossy fiber terminals
    and CA3 pyramidal neurons in rat hippocampus. Millimolar concentrations of both
    the fast Ca^2+ chelator BAPTA [1,2-bis(2-aminophenoxy)ethane- N,N, N′,N′-tetraacetic
    acid] and the slow chelator EGTA efficiently suppressed transmitter release, indicating
    loose coupling between Ca^2+ channels and release sensors. Loose coupling enabled
    the control of initial release probability by fast endogenous Ca^2+ buffers and
    the generation of facilitation by buffer saturation. Thus, loose coupling provides
    the molecular framework for presynaptic plasticity.
author:
- first_name: Nicholas
  full_name: Vyleta, Nicholas
  id: 36C4978E-F248-11E8-B48F-1D18A9856A87
  last_name: Vyleta
- 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: Vyleta N, Jonas PM. Loose coupling between Ca^2+ channels and release sensors
    at a plastic hippocampal synapse. <i>Science</i>. 2014;343(6171):665-670. doi:<a
    href="https://doi.org/10.1126/science.1244811">10.1126/science.1244811</a>
  apa: Vyleta, N., &#38; Jonas, P. M. (2014). Loose coupling between Ca^2+ channels
    and release sensors at a plastic hippocampal synapse. <i>Science</i>. American
    Association for the Advancement of Science. <a href="https://doi.org/10.1126/science.1244811">https://doi.org/10.1126/science.1244811</a>
  chicago: Vyleta, Nicholas, and Peter M Jonas. “Loose Coupling between Ca^2+ Channels
    and Release Sensors at a Plastic Hippocampal Synapse.” <i>Science</i>. American
    Association for the Advancement of Science, 2014. <a href="https://doi.org/10.1126/science.1244811">https://doi.org/10.1126/science.1244811</a>.
  ieee: N. Vyleta and P. M. Jonas, “Loose coupling between Ca^2+ channels and release
    sensors at a plastic hippocampal synapse,” <i>Science</i>, vol. 343, no. 6171.
    American Association for the Advancement of Science, pp. 665–670, 2014.
  ista: Vyleta N, Jonas PM. 2014. Loose coupling between Ca^2+ channels and release
    sensors at a plastic hippocampal synapse. Science. 343(6171), 665–670.
  mla: Vyleta, Nicholas, and Peter M. Jonas. “Loose Coupling between Ca^2+ Channels
    and Release Sensors at a Plastic Hippocampal Synapse.” <i>Science</i>, vol. 343,
    no. 6171, American Association for the Advancement of Science, 2014, pp. 665–70,
    doi:<a href="https://doi.org/10.1126/science.1244811">10.1126/science.1244811</a>.
  short: N. Vyleta, P.M. Jonas, Science 343 (2014) 665–670.
date_created: 2018-12-11T11:56:27Z
date_published: 2014-02-01T00:00:00Z
date_updated: 2021-01-12T06:56:09Z
day: '01'
department:
- _id: PeJo
doi: 10.1126/science.1244811
ec_funded: 1
intvolume: '       343'
issue: '6171'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3617475/
month: '02'
oa: 1
oa_version: Submitted Version
page: 665 - 670
project:
- _id: 25C26B1E-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P24909-B24
  name: Mechanisms of transmitter release at GABAergic synapses
- _id: 25C0F108-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '268548'
  name: Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons
publication: Science
publication_identifier:
  issn:
  - '00368075'
publication_status: published
publisher: American Association for the Advancement of Science
publist_id: '4732'
quality_controlled: '1'
scopus_import: 1
status: public
title: Loose coupling between Ca^2+ channels and release sensors at a plastic hippocampal
  synapse
type: journal_article
user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87
volume: 343
year: '2014'
...
---
_id: '3121'
abstract:
- lang: eng
  text: Voltage-activated Ca(2+) channels (VACCs) mediate Ca(2+) influx to trigger
    action potential-evoked neurotransmitter release, but the mechanism by which Ca(2+)
    regulates spontaneous transmission is unclear. We found that VACCs are the major
    physiological triggers for spontaneous release at mouse neocortical inhibitory
    synapses. Moreover, despite the absence of a synchronizing action potential, we
    found that spontaneous fusion of a GABA-containing vesicle required the activation
    of multiple tightly coupled VACCs of variable type.
acknowledgement: "The work was supported by the US National Institutes of Health (DA027110
  and GM097433) and OCTRI. C.W. and N.P.V. were supported by a grant from the National
  Heart, Lung, and Blood Institute (T32HL033808).\r\nWe thank M. Andresen and K. Khodakhah
  for helpful comments. "
author:
- first_name: Courtney
  full_name: Williams, Courtney
  last_name: Williams
- first_name: Wenyan
  full_name: Chen, Wenyan
  last_name: Chen
- first_name: Chia
  full_name: Lee, Chia
  last_name: Lee
- first_name: Daniel
  full_name: Yaeger, Daniel
  last_name: Yaeger
- first_name: Nicholas
  full_name: Vyleta, Nicholas
  id: 36C4978E-F248-11E8-B48F-1D18A9856A87
  last_name: Vyleta
- first_name: Stephen
  full_name: Smith, Stephen
  last_name: Smith
citation:
  ama: Williams C, Chen W, Lee C, Yaeger D, Vyleta N, Smith S. Coactivation of multiple
    tightly coupled calcium channels triggers spontaneous release of GABA. <i>Nature
    Neuroscience</i>. 2012;15(9):1195-1197. doi:<a href="https://doi.org/10.1038/nn.3162">10.1038/nn.3162</a>
  apa: Williams, C., Chen, W., Lee, C., Yaeger, D., Vyleta, N., &#38; Smith, S. (2012).
    Coactivation of multiple tightly coupled calcium channels triggers spontaneous
    release of GABA. <i>Nature Neuroscience</i>. Nature Publishing Group. <a href="https://doi.org/10.1038/nn.3162">https://doi.org/10.1038/nn.3162</a>
  chicago: Williams, Courtney, Wenyan Chen, Chia Lee, Daniel Yaeger, Nicholas Vyleta,
    and Stephen Smith. “Coactivation of Multiple Tightly Coupled Calcium Channels
    Triggers Spontaneous Release of GABA.” <i>Nature Neuroscience</i>. Nature Publishing
    Group, 2012. <a href="https://doi.org/10.1038/nn.3162">https://doi.org/10.1038/nn.3162</a>.
  ieee: C. Williams, W. Chen, C. Lee, D. Yaeger, N. Vyleta, and S. Smith, “Coactivation
    of multiple tightly coupled calcium channels triggers spontaneous release of GABA,”
    <i>Nature Neuroscience</i>, vol. 15, no. 9. Nature Publishing Group, pp. 1195–1197,
    2012.
  ista: Williams C, Chen W, Lee C, Yaeger D, Vyleta N, Smith S. 2012. Coactivation
    of multiple tightly coupled calcium channels triggers spontaneous release of GABA.
    Nature Neuroscience. 15(9), 1195–1197.
  mla: Williams, Courtney, et al. “Coactivation of Multiple Tightly Coupled Calcium
    Channels Triggers Spontaneous Release of GABA.” <i>Nature Neuroscience</i>, vol.
    15, no. 9, Nature Publishing Group, 2012, pp. 1195–97, doi:<a href="https://doi.org/10.1038/nn.3162">10.1038/nn.3162</a>.
  short: C. Williams, W. Chen, C. Lee, D. Yaeger, N. Vyleta, S. Smith, Nature Neuroscience
    15 (2012) 1195–1197.
date_created: 2018-12-11T12:01:30Z
date_published: 2012-09-01T00:00:00Z
date_updated: 2021-01-12T07:41:12Z
day: '01'
department:
- _id: PeJo
doi: 10.1038/nn.3162
external_id:
  pmid:
  - '22842148'
intvolume: '        15'
issue: '9'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431448/
month: '09'
oa: 1
oa_version: Submitted Version
page: 1195 - 1197
pmid: 1
publication: Nature Neuroscience
publication_status: published
publisher: Nature Publishing Group
publist_id: '3578'
quality_controlled: '1'
scopus_import: 1
status: public
title: Coactivation of multiple tightly coupled calcium channels triggers spontaneous
  release of GABA
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 15
year: '2012'
...
---
_id: '469'
abstract:
- lang: eng
  text: 'Spontaneous release of glutamate is important for maintaining synaptic strength
    and controlling spike timing in the brain. Mechanisms regulating spontaneous exocytosis
    remain poorly understood. Extracellular calcium concentration ([Ca2+]o) regulates
    Ca2+ entry through voltage-activated calcium channels (VACCs) and consequently
    is a pivotal determinant of action potential-evoked vesicle fusion. Extracellular
    Ca 2+ also enhances spontaneous release, but via unknown mechanisms. Here we report
    that external Ca2+ triggers spontaneous glutamate release more weakly than evoked
    release in mouse neocortical neurons. Blockade of VACCs has no effect on the spontaneous
    release rate or its dependence on [Ca2+]o. Intracellular [Ca2+] slowly increases
    in a minority of neurons following increases in [Ca2+]o. Furthermore, the enhancement
    of spontaneous release by extracellular calcium is insensitive to chelation of
    intracellular calcium by BAPTA. Activation of the calcium-sensing receptor (CaSR),
    a G-protein-coupled receptor present in nerve terminals, by several specific agonists
    increased spontaneous glutamate release. The frequency of spontaneous synaptic
    transmission was decreased in CaSR mutant neurons. The concentration-effect relationship
    for extracellular calcium regulation of spontaneous release was well described
    by a combination of CaSR-dependent and CaSR-independent mechanisms. Overall these
    results indicate that extracellular Ca2+ does not trigger spontaneous glutamate
    release by simply increasing calcium influx but stimulates CaSR and thereby promotes
    resting spontaneous glutamate release. '
author:
- first_name: Nicholas
  full_name: Vyleta, Nicholas
  id: 36C4978E-F248-11E8-B48F-1D18A9856A87
  last_name: Vyleta
- first_name: Stephen
  full_name: Smith, Stephen
  last_name: Smith
citation:
  ama: Vyleta N, Smith S. Spontaneous glutamate release is independent of calcium
    influx and tonically activated by the calcium-sensing receptor. <i>European Journal
    of Neuroscience</i>. 2011;31(12):4593-4606. doi:<a href="https://doi.org/10.1523/JNEUROSCI.6398-10.2011">10.1523/JNEUROSCI.6398-10.2011</a>
  apa: Vyleta, N., &#38; Smith, S. (2011). Spontaneous glutamate release is independent
    of calcium influx and tonically activated by the calcium-sensing receptor. <i>European
    Journal of Neuroscience</i>. Wiley-Blackwell. <a href="https://doi.org/10.1523/JNEUROSCI.6398-10.2011">https://doi.org/10.1523/JNEUROSCI.6398-10.2011</a>
  chicago: Vyleta, Nicholas, and Stephen Smith. “Spontaneous Glutamate Release Is
    Independent of Calcium Influx and Tonically Activated by the Calcium-Sensing Receptor.”
    <i>European Journal of Neuroscience</i>. Wiley-Blackwell, 2011. <a href="https://doi.org/10.1523/JNEUROSCI.6398-10.2011">https://doi.org/10.1523/JNEUROSCI.6398-10.2011</a>.
  ieee: N. Vyleta and S. Smith, “Spontaneous glutamate release is independent of calcium
    influx and tonically activated by the calcium-sensing receptor,” <i>European Journal
    of Neuroscience</i>, vol. 31, no. 12. Wiley-Blackwell, pp. 4593–4606, 2011.
  ista: Vyleta N, Smith S. 2011. Spontaneous glutamate release is independent of calcium
    influx and tonically activated by the calcium-sensing receptor. European Journal
    of Neuroscience. 31(12), 4593–4606.
  mla: Vyleta, Nicholas, and Stephen Smith. “Spontaneous Glutamate Release Is Independent
    of Calcium Influx and Tonically Activated by the Calcium-Sensing Receptor.” <i>European
    Journal of Neuroscience</i>, vol. 31, no. 12, Wiley-Blackwell, 2011, pp. 4593–606,
    doi:<a href="https://doi.org/10.1523/JNEUROSCI.6398-10.2011">10.1523/JNEUROSCI.6398-10.2011</a>.
  short: N. Vyleta, S. Smith, European Journal of Neuroscience 31 (2011) 4593–4606.
date_created: 2018-12-11T11:46:39Z
date_published: 2011-03-23T00:00:00Z
date_updated: 2021-01-12T08:00:49Z
day: '23'
department:
- _id: PeJo
doi: 10.1523/JNEUROSCI.6398-10.2011
intvolume: '        31'
issue: '12'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3097128/
month: '03'
oa: 1
oa_version: Submitted Version
page: 4593 - 4606
publication: European Journal of Neuroscience
publication_status: published
publisher: Wiley-Blackwell
publist_id: '7353'
quality_controlled: '1'
scopus_import: 1
status: public
title: Spontaneous glutamate release is independent of calcium influx and tonically
  activated by the calcium-sensing receptor
type: journal_article
user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87
volume: 31
year: '2011'
...