Cited by 197Neuroscience and Neuropharmacology ResearchNeural dynamics and brain functionCellular transport and secretion

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Properties of Quantal Transmission at CA1 Synapses

Raghavachari, Sridhar, Lisman, John E.·2004·Journal of Neurophysiology

DOI 10.1152/jn.00258.2004

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Abstract

We have used Monte Carlo simulations to understand the generation of quantal responses at the single active zones of CA1 synapses. We constructed a model of AMPA channel activation that accounts for the responses to controlled glutamate application and a model of glutamate diffusion in the synaptic cleft. With no further adjustments to these models, we simulated the response to the release of glutamate from a single vesicle. The predicted response closely matches the rise time of observed responses, which recent measurements show is much faster (<100 micros) than previously thought. The simulations show that initial channel opening is driven by a brief (<100 micros) glutamate spike near the site of vesicle fusion, producing a hotspot of channel activation (diameter: approximately 250 nm) smaller than many synapses. Quantal size therefore depends more strongly on the density of channels than their number, a finding that has important implications for measuring synaptic strength. Recent measurements allow estimation of AMPA receptor density at CA1 synapses. Using this value, our simulations correctly predicts a quantal amplitude of approximately 10 pA. We have also analyzed the properties of excitatory postsynaptic currents (EPSCs) generated by the multivesicular release that can occur during evoked responses. We find that summation is nearly linear and that the existence of multiple narrow peaks in amplitude histograms can be accounted for. It has been unclear how to reconcile…

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Authors: Raghavachari, S., & Lisman, J. E.
Affiliations: Brandeis University (US)
ORCID: Lisman, John E.
Venue: Journal of Neurophysiology
Publisher: American Physiological Society
Published: 2004-10
Volume: 92
Issue: 4
Pages: 2456-2467
ISSN: 0022-3077 (ISSN-L)
1522-1598
DOI: 10.1152/jn.00258.2004
OpenAlex: W2115645299
Cited by: 197
References: 96
Citations by year: 2026: 3 · 2025: 9 · 2024: 11 · 2023: 9 · 2022: 7 · 2021: 15 · 2020: 8 · 2019: 7 · 2018: 10 · 2017: 13 · 2016: 10 · 2015: 13 · 2014: 5 · 2013: 8 · 2012: 13
FWCI: 1.52
Type: journal article
Language: en
Open access: closed
Locations: Journal of Neurophysiology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01ns035083-04)
National Institute of Neurological Disorders and Stroke (R01NS027337, R01 NS27337, R01 NS35083)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords: CA1 synapses, AMPA receptors, glutamate diffusion, synaptic cleft, vesicle fusion, miniature EPSCs, multivesicular release, synaptic efficacy, channel density, rise time
MeSH terms: Benzothiadiazines, Computer Simulation, Diuretics, Hippocampus, Kinetics, Monte Carlo Method, Synaptic Transmission, Stochastic Processes, Synapses, Neural Networks, Computer, Receptors, AMPA, Glutamic Acid, Excitatory Postsynaptic Potentials

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Properties of Quantal Transmission at CA1 Synapses

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