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Independent Sources of Quantal Variability at Single Glutamatergic Synapses
Open accessAbstract
Variability in the size of single postsynaptic responses is a feature of most central neurons, although the source of this variability is not completely understood. The dominant source of variability could be either intersynaptic or intrasynaptic. To quantitatively examine this question, a biophysically realistic model of an idealized central axospinous synapse was used to assess mechanisms underlying synaptic variability measurements. Three independent sources of variability were considered: stochasticity of postsynaptic receptors ("channel noise"), variations of glutamate concentration in the synaptic cleft (Deltaq), and differences in the potency of vesicles released from different locations on the active zone [release-location dependence (RLD)]. As expected, channel noise was small (8% of the total variance) and Deltaq was the dominant source of variability (58% of total variance). Surprisingly, RLD accounted for a significant amount of variability (36%). Our simulations show that potency of release sites decreased with a length constant of approximately 100 nm, and that receptors were not activated by release events >300 nm away, which is consistent with the observation that single active zones are rarely >300 nm. RLD also predicts that the manner in which receptors are added or removed from synapses can dramatically affect the nature of the synaptic response, with increasing receptor density being more efficient than merely increasing synaptic area. Saturation levels and synaptic geometry were also important in determining the size and shape of the distribution of amplitudes recorded at different synapses.
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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 [3]
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“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 [3]
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Metadata
- Authors
- Franks, K. M., Stevens, C. F., & Sejnowski, T. J.
- Affiliations
- Howard Hughes Medical Institute (US)
- Salk Institute for Biological Studies (US)
- ORCID
- Stevens, Charles F.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2003-04-15
- Volume
- 23
- Issue
- 8
- Pages
- 3186-3195
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2944019
- OpenAlex
- W2148126095
- Cited by
- 224
- References
- 55
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 17 · 2023: 7 · 2022: 9 · 2021: 14 · 2020: 6 · 2019: 11 · 2018: 10 · 2017: 8 · 2016: 7 · 2015: 16 · 2014: 10 · 2013: 11 · 2012: 14
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Howard Hughes Medical Institute
- 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
- synaptic variability, glutamatergic synapses, channel noise, active zone, synaptic vesicle release, receptor saturation
- MeSH terms
- Biophysics, Computer Simulation, Models, Neurological, Monte Carlo Method, Synaptic Transmission, Particle Size, Stochastic Processes, Synapses, Synaptic Vesicles, Reproducibility of Results, Receptors, N-Methyl-D-Aspartate, Receptors, AMPA, Glutamic Acid, Excitatory Postsynaptic Potentials
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