The DOI matches its Crossref record; 94 of the 96 references it cites were found in a registry or an index.
Properties of Quantal Transmission at CA1 Synapses
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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“given that the probability of AMPAR activation declines with distance from glutamate release sites has previously been deduced3,16”
From A trans-synaptic nanocolumn aligns neurotransmitter release to receptors (2016) · cites this paper as [16]
In the citing paper
“Central to this approach is the relationship between channel opening probability and its distance from a release site, determined previously by stochastic modeling approaches3,16,47: (6)Po(r)=0.42e-r/88nm”
From A trans-synaptic nanocolumn aligns neurotransmitter release to receptors (2016) · cites this paper as [16]
Citations
Cites
Glutamate receptor ion channels
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The Glutamate Receptor Ion Channels
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Matsuzaki, M., Ellis-Davies, G. C. R., Nemoto, T., Miyashita, Y., Iino, M., & Kasai, H. (2001) · Nature Neuroscience · doi:10.1038/nn736 · Cited by 1,563 · cited 4×
“…presynaptic release using FM dyes (Zakharenko et al. 2002) and the postsynaptic contribution to synaptic strength using two-photon glutamate uncaging are becoming available (Matsuzaki et al. 2001; Smith et al. 2003) , which will greatly enhance our understanding of quantal transmission at synapses.”
BackgroundMethodInfluentialStructure and function of dendritic spines
Nimchinsky, E. A., Sabatini, B. L., & Svoboda, K. (2002) · Annual Review of Physiology · doi:10.1146/annurev.physiol.64.081501.160008 · Cited by 1,208
Heterogeneity of release probability, facilitation, and depletion at central synapses
Dobrunz, L. E., & Stevens, C. F. (1997) · Neuron · doi:10.1016/s0896-6273(00)80338-4 · Cited by 1,183
The Time Course of Glutamate in the Synaptic Cleft
Clements, J. D., Lester, R. A. J., Tong, G., Jahr, C. E., & Westbrook, G. L. (1992) · Science · doi:10.1126/science.1359647 · Cited by 1,089
Harris, K., & Stevens, J. (1989) · The Journal of Neuroscience · doi:10.1523/jneurosci.09-08-02982.1989 · Cited by 1,073
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Quantitative ultrastructural analysis of hippocampal excitatory synapses
Schikorski, T., & Stevens, C. F. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-15-05858.1997 · Cited by 997
Mechanisms for Activation and Antagonism of an AMPA-Sensitive Glutamate Receptor
Armstrong, N., & Gouaux, E. (2000) · Neuron · doi:10.1016/s0896-6273(00)00094-5 · Cited by 874
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2 of the 96 references couldn’t be matched to a known paper.
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Actin in action: the interplay between the actin cytoskeleton and synaptic efficacy.
Cingolani, L. A., & Goda, Y. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2373 · Cited by 831
A trans-synaptic nanocolumn aligns neurotransmitter release to receptors
Tang, A.-H., Chen, H., Li, T. P., Metzbower, S. R., MacGillavry, H. D., & Blanpied, T. A. (2016) · Nature · doi:10.1038/nature19058 · Cited by 677
Nair, D., Hosy, E., Petersen, J. D., Constals, A., Giannone, G., Choquet, D., & Sibarita, J.-B. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.2381-12.2013 · Cited by 617
Nanoscale Scaffolding Domains within the Postsynaptic Density Concentrate Synaptic AMPA Receptors
MacGillavry, H. D., Song, Y., Raghavachari, S., & Blanpied, T. A. (2013) · Neuron · doi:10.1016/j.neuron.2013.03.009 · Cited by 442
Self-citationStructural and Functional Architecture of AMPA-Type Glutamate Receptors and Their Auxiliary Proteins
Greger, I. H., Watson, J. F., & Cull-Candy, S. G. (2017) · Neuron · doi:10.1016/j.neuron.2017.04.009 · Cited by 392
Metadata
- 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
- 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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