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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The probability of AMPA receptor activation declines with distance from glutamate release sites.
“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]
The relationship between channel opening probability and distance from a release site is Po(r)=0.42e-r/88nm.
“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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Functional organization of postsynaptic glutamate receptors
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“…that the probability of AMPAR opening is highest near vesicle release sites, producing local hotspots (< 0.03 μ m 2 ) of maximally activated AMPARs that cover only a fraction of the total PSD area (~25% of an average PSD in a CA1 synapse) (Franks et al., 2003; Raghavachari and Lisman, 2004).”
InfluentialTheoretical models of synaptic short term plasticity
Hennig, M. H. (2013) · Frontiers in Computational Neuroscience · doi:10.3389/fncom.2013.00154 · Cited by 148 · see citing works
“The interplay of these factors with synapse morphology has been investigated in great detail with Monte Carlo simulations (Stiles et al., 1996; Franks et al., 2003; Coggan et al., 2005; Postlethwaite et al., 2007), which are in particular useful to understand the sources of variability at synapses.”
Matsui, K., Jahr, C. E., & Rubio, M. E. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.1927-05.2005 · Cited by 143 · see citing works
“Most diffusion models predict that the extrasynaptic concentrations of transmitter attained by diffusion out of the cleft are relatively small (Eccles and Jaeger, 1958; Barbour, 2001; Franks et al., 2003).”
BackgroundZawisza, I. A., Rózga, M., & Bal, W. (2012) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2012.03.012 · Cited by 138 · see citing works
Influence of Synaptic Vesicle Position on Release Probability and Exocytotic Fusion Mode
Park, H., Li, Y., & Tsien, R. W. (2012) · Science · doi:10.1126/science.1216937 · Cited by 131 · see citing works
How Does Neuroscience Affect Our Conception of Volition?
Roskies, A. L. (2010) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-060909-153151 · Cited by 125 · see citing works
“…on choice may be a vestige of an implicit dualism between the mentalism of choice and the physicalism of action, the processes underlying decision as a means for forming intentions seem to be a central aspect of volition even if one rejects dualism, as most contemporary philosophers and…”
BackgroundOptogenetic Control of Synaptic Composition and Function
Sinnen, B. L., Bowen, A. B., Forte, J. S., Hiester, B. G., Crosby, K. C., Gibson, E. S., Dell’Acqua, M. L., & Kennedy, M. J. (2017) · Neuron · doi:10.1016/j.neuron.2016.12.037 · Cited by 124 · see citing works
“Given the low affinity of AMPA receptors for glutamate, models of quantal synaptic transmission restrict postsynaptic AMPA receptor activation to subsynaptic hotspots, 250 nm in diameter, apposed to presynaptic vesicle release sites (Franks et al., 2003; Raghavachari and Lisman, 2004).”
Tong, X.-J., Soto, E. J. L., Li, L., Liu, H., Nedelcu, D., Lipscombe, D., Hu, Z., & Kaplan, J. M. (2017) · Neuron · doi:10.1016/j.neuron.2017.06.018 · Cited by 116 · see citing works
“Coupling would optimally localize clustered receptors within the post-synaptic density so that they could be efficiently activated by SV fusion (Franks et al., 2003).”
Tarusawa, E., Matsui, K., Budisantoso, T., Molnár, E., Watanabe, M., Matsui, M., Fukazawa, Y., & Shigemoto, R. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.6160-08.2009 · Cited by 118 · see citing works
“As morphological characteristics including receptor distributions have been suggested to influence synaptic property (Franks et al., 2002, 2003; Xu-Friedman and Regehr, 2004), it appeared conceivable that vesicular release of glutamate in close proximity to AMPAR microclusters would result in…”
BackgroundMethodInfluentialDoi, T., Kuroda, S., Michikawa, T., & Kawato, M. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2727-04.2005 · Cited by 117 · see citing works
Super-resolving Microscopy in Neuroscience
Werner, C. D., Sauer, M., & Geis, C. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c01174 · Cited by 111 · see citing works
The Origin of Quantal Size Variation: Vesicular Glutamate Concentration Plays a Significant Role
Wu, X.-S., Xue, L., Mohan, R., Paradiso, K. G., Gillis, K. D., & Wu, L. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.4415-06.2007 · Cited by 107 · see citing works
“…size variation Higher glutamate concentrations experienced by postsynaptic receptors could be caused by either a larger amount of released transmitter or a shorter distance (distancefusion_receptor) between the fusion site and the center of the postsynaptic receptor cluster (Franks et al., 2003).”
BackgroundPostfusional Control of Quantal Current Shape
Pawlu, C., DiAntonio, A., & Heckmann, M. (2004) · Neuron · doi:10.1016/s0896-6273(04)00269-7 · Cited by 110 · see citing works
Probabilistic Neural Computing with Stochastic Devices
Misra, S., Bland, L. C., Cardwell, S., Incorvia, J. A. C., James, C. D., Kent, A. D., Schuman, C. D., Smith, J. D., & Aimone, J. B. (2022) · Advanced Materials · doi:10.1002/adma.202204569 · Cited by 107 · see citing works
Paired-pulse depression of unitary quantal amplitude at single hippocampal synapses
Chen, G., Harata, N. C., & Tsien, R. W. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307149101 · Cited by 102 · see citing works
Ion Channels Set Spike Timing Regularity of Mammalian Vestibular Afferent Neurons
Kalluri, R., Xue, J., & Eatock, R. A. (2010) · Journal of Neurophysiology · doi:10.1152/jn.00396.2010 · Cited by 102 · see citing works
Calmodulin Activation by Calcium Transients in the Postsynaptic Density of Dendritic Spines
Keller, D. X., Franks, K. M., Bartol, T. M., & B, T. J. S. A. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002045 · Cited by 94 · see citing works
“The activation of postsynaptic NMDA receptors by glutamate released in an idealized, 3D neuropil has been described elsewhere [31,32,33].”
BackgroundSelf-citationThe ubiquitous nature of multivesicular release
Rudolph, S., Tsai, M., von Gersdorff, H., & Wadiche, J. I. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.05.008 · Cited by 95 · see citing works
Subsynaptic positioning of AMPARs by LRRTM2 controls synaptic strength
Ramsey, A. M., Tang, A., LeGates, T. A., Gou, X., Carbone, B. E., Thompson, S. M., Biederer, T., & Blanpied, T. A. (2021) · Science Advances · doi:10.1126/sciadv.abf3126 · Cited by 90 · see citing works
Intracellular Chloride Channels: Determinants of Function in the Endosomal Pathway
Faúndez, V., & Hartzell, H. C. (2004) · Science s STKE · doi:10.1126/stke.2332004re8 · Cited by 91 · see citing works
Kerr, J. M., & Blanpied, T. A. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.2927-11.2012 · Cited by 91 · see citing works
“For these reasons, the distribution of AMPARs within a synapse is broadly thought to influence synaptic efficacy (Xie et al., 1997; Franks et al., 2003; Raghavachari and Lisman, 2004; Lisman et al., 2007).”
BackgroundPostlethwaite, M., Hennig, M. H., Steinert, J. R., Graham, B. P., & Forsythe, I. D. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.123612 · Cited by 87 · see citing works
“To reproduce the observed variability of mEPSCs (see Results; Franks et al. 2003; Raghavachari & Lisman, 2004), the precise location of the vesicle was assumed to be uniformly distributed over an area restricted to 200 nm relative to the centre of this PSD.”
BackgroundInfluentialSynapse Geometry and Receptor Dynamics Modulate Synaptic Strength
Freche, D., Pannasch, U., Rouach, N., & Holcman, D. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025122 · Cited by 86 · see citing works
“2μm(2)/ms [7] was used in all simulations, we here explore the effect on glutamate spreading and uptake for a doubled diffusion constant Ddouble = 0.”
MethodBuonarati, O. R., Hammes, E. A., Watson, J. F., Greger, I. H., & Hell, J. W. (2019) · Science Signaling · doi:10.1126/scisignal.aar6889 · Cited by 81 · see citing works
“The importance of precise postsynaptic localization of AMPARs Because the affinity of AMPARs for glutamate is relatively low (high micromolar range), it had been predicted that only AMPARs that are precisely juxtaposed to presynaptic release sites are effectively activated (84, 85).”
BackgroundAstrocytes Optimize the Synaptic Transmission of Information
Nadkarni, S., Jung, P., & Levine, H. (2008) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000088 · Cited by 77 · see citing works
“Amongst them reduction in vesicular glutamate concentration (quantal size) and receptor desensitization play a significant role in lowering the amplitude of the postsynaptic response at central glutamatergic synapses [7–10].”
Noisy Synaptic Conductance: Bug or a Feature?
Rusakov, D. A., Savtchenko, L. P., & Latham, P. E. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.03.009 · Cited by 75 · see citing works
“Second, synaptic receptor binding and activation is a stochastic process controlled by conformational changes of receptor proteins [22,23].”
BackgroundMedalla, M., & Luebke, J. I. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.3426-14.2015 · Cited by 71 · see citing works
“…an EPSC, the areal spread of glutamate from a single vesicle covers 0.04 – 0.05 m 2 of the PSD area (Clements et al., 1992; Diamond and Jahr, 1997; Franks et al., 2003; Raghavachari and Lisman, 2004), which can saturate AMPA receptors on small simple synapses but not on large perforated…”
BackgroundInfluentialBell, M. E., Bourne, J. N., Chirillo, M. A., Mendenhall, J. M., Kuwajima, M., & Harris, K. M. (2014) · Journal of Comparative Neurology · doi:10.1002/cne.23646 · Cited by 72 · see citing works
“These measurements suggest that an AMPAR in a nascent zone would have a much lower probability of response than AMPARs anchored beneath docking sites in the active zone (Franks et al., 2003).”
BackgroundMethodInfluentialTheoretical models of synaptic short term plasticity
Hennig, M. H. (2013) · Frontiers in Computational Neuroscience · doi:10.3389/fncom.2013.00045 · Cited by 72 · see citing works
“A drawback of this approach is that this also requires an appropriate model of the time course of neurotransmitter seen by the receptors, which has to be obtained by more detailed diffusion models (see e.g., Franks et al., 2003; Postlethwaite et al., 2007).”
BackgroundMethodPatriarchi, T., Buonarati, O. R., & Hell, J. W. (2018) · The EMBO Journal · doi:10.15252/embj.201899771 · Cited by 65 · see citing works
“Localization of AMPARs in those nanoclusters is thought to be functionally important because affinity of AMPARs for glutamate is fairly low and only AMPARs that are exactly juxtaposed to presynaptic release sites might be effectively activated (Franks et al, 2003; Lisman & Raghavachari, 2006).”
Effects of nanoplastic exposure during pregnancy and lactation on neurodevelopment of rat offspring
Tian, L., Zhang, Y., Chen, J., Liu, X., Nie, H., Li, K., Liu, H., Lai, W., Shi, Y., Xi, Z., et al. (2024) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2024.134800 · Cited by 66 · see citing works
Lateral organization of the postsynaptic density
MacGillavry, H. D., Kerr, J. M., & Blanpied, T. A. (2011) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2011.09.001 · Cited by 64 · see citing works
“…factors, numerical modeling suggests that while AMPA receptors directly across from the site of release open with fairly high probability (~0.6), receptors laterally displaced by even 50 nm are much less likely to open (Franks et al., 2003; Raghavachari and Lisman, 2004; Xie et al., 1997).”
BackgroundInfluentialLocal diffusion in the extracellular space of the brain
Tønnesen, J., Hrabětová, S., & Soria, F. N. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105981 · Cited by 64 · see citing works
Protein Crowding within the Postsynaptic Density Can Impede the Escape of Membrane Proteins
Li, T. P., Song, Y., MacGillavry, H. D., Blanpied, T. A., & Raghavachari, S. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.3154-15.2016 · Cited by 63 · see citing works
“Synaptic strength is modulated by both the density and positioning of AMPARs within the synapse (Xie et al., 1997; Franks et al., 2003; Raghavachari and Lisman, 2004; Lisman et al., 2007; Kessels and Malinow, 2009), so determining the mechanisms that establish their synaptic entry, exit, and…”
BackgroundSuper-resolution microscopy: a closer look at synaptic dysfunction in Alzheimer disease
Padmanabhan, P., Kneynsberg, A., & Götz, J. (2021) · Nature reviews. Neuroscience · doi:10.1038/s41583-021-00531-y · Cited by 55 · see citing works
Evaluation of glutamate concentration transient in the synaptic cleft of the rat calyx of Held
Budisantoso, T., Harada, H., Kamasawa, N., Fukazawa, Y., Shigemoto, R., & Matsui, K. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2012.241398 · Cited by 59 · see citing works
“Although theoretical studies have realized that a steep gradient of glutamate concentration is created within the synapse (Trommershäuser et al. 1999; Franks et al. 2003), to understand the effect of such a gradient on postsynaptic response, knowledge of the distribution of the receptors within the cleft was needed.”
BackgroundInfluentialDiffusion-Based Model for Synaptic Molecular Communication Channel
Khan, T., Bilgin, B. A., & Akan, Ö. B. (2017) · IEEE Transactions on NanoBioscience · doi:10.1109/tnb.2017.2707482 · Cited by 58 · see citing works
“Consequently, major sources of trial-to-trial variability [21] in single postsynaptic response are discussed.”
BackgroundCreating diverse synapses from the same molecules
Nusser, Z. (2018) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2018.01.001 · Cited by 63 · see citing works
“What could be the functional consequences of such distinct sub-synaptic distributions? Monte Carlo simulations of glutamatergic synapses indicated that the location of vesicle fusion within the active zone (AZ) affects postsynaptic AMPAR open probability (Po), indicating that AMPAR unevenness within the PSD would have…”
BackgroundMechanisms Underlying Signal Filtering at a Multisynapse Contact
Budisantoso, T., Matsui, K., Kamasawa, N., Fukazawa, Y., & Shigemoto, R. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.5243-11.2012 · Cited by 56 · see citing works
“…activation from the release site (half-width at halfmaximum distance of peak Po 125 nm; see previous simulations for comparison) (Barbour, 2001; Franks et al., 2003; Raghavachari and Lisman, 2004; Tarusawa et al., 2009) matches well with the extent of AMPAR distribution (50% cumulative…”
BackgroundInfluentialBywalez, W. G., Patirniche, D., Rupprecht, V., Stemmler, M., Herz, A. V. M., Pálfi, D., Rózsa, B. J., & Egger, V. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.051 · Cited by 55 · see citing works
Sun, Y., Smirnov, M., Kamasawa, N., & Yasuda, R. (2021) · The Journal of Neuroscience · doi:10.1523/jneurosci.1964-20.2021 · Cited by 51 · see citing works
“AMPARs exist in extrasynaptic membrane near the PSD (Tao-Cheng et al., 2011; Nair et al., 2013) and likely were able to support synaptic transmission (Franks et al., 2003; Tardin et al., 2003), although their contribution to synaptic transmission is expected to be smaller (Franks et al., 2003).”
BackgroundResultHarris, K. M., Špaček, J., Bell, M. E., Parker, P. H., Lindsey, L. F., Baden, A. D., Vogelstein, J. T., & Burns, R. C. (2015) · Scientific Data · doi:10.1038/sdata.2015.46 · Cited by 51 · see citing works
Zampini, V., Johnson, S. L., Franz, C., Knipper, M., Holley, M. C., Magistretti, J., Masetto, S., & Marcotti, W. (2013) · The Journal of Physiology · doi:10.1113/jphysiol.2013.251272 · Cited by 49 · see citing works
“…findings showed that the amplitude of EPSCs is independent of presynaptic Ca2+ influx (Glowatzki & Fuchs, 2002; Grant et al. 2010), indicating that postsynaptic mechanisms could also contribute to the highly variable EPSC amplitude, as proposed for central glutamate synapses (Franks et al. 2003).”
BackgroundModerate AMPA receptor clustering on the nanoscale can efficiently potentiate synaptic current
Savtchenko, L. P., & Rusakov, D. A. (2013) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2013.0167 · Cited by 49 · see citing works
Heterogeneity of glutamatergic synapses: cellular mechanisms and network consequences
Wichmann, C., & Kuner, T. (2021) · Physiological Reviews · doi:10.1152/physrev.00039.2020 · Cited by 59 · see citing works
Specificity of Primate Amygdalar Pathways to Hippocampus
Wang, J., & Barbas, H. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.1267-18.2018 · Cited by 48 · see citing works
“Previous studies have shown that quantal release of neurotransmitter is sufficient to saturate AMPA receptors within a postsynaptic area of 0.04 – 0.05 m 2 (Franks et al., 2003; Raghavachari and Lisman, 2004; Medalla and Luebke, 2015).”
BackgroundInfluentialIndividual synaptic vesicles mediate stimulated exocytosis from cochlear inner hair cells
Grabner, C. P., & Moser, T. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1811814115 · Cited by 47 · see citing works
“(36) modeled different presynaptic and postsynaptic arrangements for a simple central synapse, and 2,000–3,000 molecules of glutamate released per SV was sufficient to yield realistic outcomes for UVR.”
BackgroundNoradrenaline Triggers Multivesicular Release at Glutamatergic Synapses in the Hypothalamus
Gordon, G. R., & Bains, J. S. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2378-05.2005 · Cited by 47 · see citing works
“, 1992), there has been strong support for a presynaptic mechanism explaining the skew in the control miniature amplitude distribution at central synapses (Frerking et al., 1995; Forti et al., 1997; Liu et al., 1999; McAllister and Stevens, 2000; Hanse and Gustafsson, 2001; Franks et al., 2003).”
BackgroundGuzman, R. E., Schwarz, Y. N., Rettig, J., & Bruns, D. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1551-10.2010 · Cited by 46 · see citing works
“Furthermore, “off-center” release should be again accompanied with a profound decrease in charge transfer per SSV signal (Franks et al., 2003; Wu et al., 2007).”
BackgroundNano-Organization at the Synapse: Segregation of Distinct Forms of Neurotransmission
Guzikowski, N. J., & Kavalali, E. T. (2021) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2021.796498 · Cited by 45 · see citing works
“…mutations drastically reduce asynchronous release and associated synaptic vesicle trafficking providing the molecular framework for the differential timing of these two types of action potential dependent release (Geppert et al., 1994; Sugita et al., 2002; Bacaj et al., 2013; Li et al., 2017).”
BackgroundA network of autism linked genes stabilizes two pools of synaptic GABAA receptors
Tong, X.-J., Hu, Z., Liu, Y., Anderson, D. C., & Kaplan, J. M. (2015) · eLife · doi:10.7554/elife.09648 · Cited by 44 · see citing works
Compans, B., Choquet, D., & Hosy, E. (2016) · Neurophotonics · doi:10.1117/1.nph.3.4.041811 · Cited by 42 · see citing works
“As mentioned above, studies in the early 2000s questioned the existence of a putative sub-PSD organization of postsynaptic proteins.(54,56,59) Unfortunately, optical microscopy is limited by diffraction to 300 nm, rendering it impossible to decipher AMPAR organization with a precision higher than the PSD size.”
BackgroundInfluentialCao, G., & Harris, K. M. (2014) · Journal of Neurophysiology · doi:10.1152/jn.00297.2014 · Cited by 41 · see citing works
Particle-Based Stochastic Simulation in Systems Biology
Tölle, D., & Novère, N. G. L. (2006) · Current Bioinformatics · doi:10.2174/157489306777827964 · Cited by 40 · see citing works
“Problems that were addressed using MCell include modeling of glutamate spill-over leading to activation of extra-synaptic receptors and buffered diffusion effects due to trapping of neurotransmitter by receptors at the glutamatergic synapse [9], or variability in the size of postsynaptic potentials caused by release o…”
BackgroundMethodTarget-Specific Regulation of Synaptic Amplitudes in the Neocortex
Watanabe, J., Rozov, A. V., & Wollmuth, L. P. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3951-04.2005 · Cited by 41 · see citing works
“In contrast, postsynaptic factors such as the distribution of postsynaptic receptors relative to the release site (Uteshev and Pennefather, 1996; Franks et al., 2003), the degree of their saturation (Mainen et al., 1999; McAllister and Stevens, 2000; Harrison and Jahr, 2003), and biophysical…”
BackgroundThe organization of AMPA receptor subunits at the postsynaptic membrane
Jacob, A., & Weinberg, R. J. (2014) · Hippocampus · doi:10.1002/hipo.22404 · Cited by 40 · see citing works
“Computational studies predict that precise alignment between presynaptic sites of glutamate release and postsynaptic receptors increases synaptic efficiency (Xie et al., 1997; Raghavachari et al., 2004; Franks et al., 2003; Freche et al., 2011; Rusakov et al., 2011; Allam et al., 2012).”
BackgroundQuantal Glutamate Release Is Essential for Reliable Neuronal Encodings in Cerebral Networks
Yu, J., Qian, H., Chen, N., & Wang, J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025219 · Cited by 39 · see citing works
“It is still not conclusive whether the fluctuations of synaptic strength under basal condition and plasticity result from the variations in the probability or the contents of transmitter release [16,18,20,23,25,26,35].”
BackgroundDistinct AMPA-Type Glutamatergic Synapses in Developing Rat CA1 Hippocampus
Stubblefield, E. A., & Benke, T. A. (2010) · Journal of Neurophysiology · doi:10.1152/jn.00099.2010 · Cited by 38 · see citing works
Asymmetry Between Pre- and Postsynaptic Transient Nanodomains Shapes Neuronal Communication
Heine, M., & Holcman, D. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.01.005 · Cited by 34 · see citing works
“Thus, the nanoscale clustering of AMPAR is activity-dependent [90–92] and confirms modeling data on subsynaptic receptor organization and their impact on the synapse performance over time [46,93].”
BackgroundTransmission Between Type II Hair Cells and Bouton Afferents in the Turtle Posterior Crista
Holt, J. C., Xue, J.-T., Brichta, A. M., & Goldberg, J. M. (2005) · Journal of Neurophysiology · doi:10.1152/jn.00447.2005 · Cited by 35 · see citing works
“A similar conclusion has been reached in studies of many single-site synapses (for review, see Franks et al. 2003).”
ResultEstimating the Readily-Releasable Vesicle Pool Size at Synaptic Connections in the Neocortex
Barros-Zulaica, N., Rahmon, J., Chindemi, G., Perin, R., Markram, H., Ramaswamy, S., & Muller, E. B. (2019) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2019.00029 · Cited by 34 · see citing works
Tölle, D., & Novère, N. G. L. (2010) · BMC Systems Biology · doi:10.1186/1752-0509-4-24 · Cited by 34 · see citing works
“Examples include analyses of glutamate release location relative to post-synaptic receptor location during neurotransmitter release in the glutamate synapse [20], or investigating the effect of signal molecule locations on signalling during bacterial chemotaxis [21].”
BackgroundThe glutamatergic synapse: a complex machinery for information processing
Maio, V. D. (2021) · Cognitive Neurodynamics · doi:10.1007/s11571-021-09679-w · Cited by 34 · see citing works
“…authors have obtained different values either for the Glu concentration (0.4 M (Karunanithi et al. 2002)) and for the estimation of the internal radius and simulation have been made with 2000 molecules of Glu (Franks et al. 2003, based on data of Karunanithi et al. (2002) obtained on Drosophila).”
BackgroundMethodInfluentialJung, J. H., Kirk, L. M., Bourne, J. N., & Harris, K. M. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2018653118 · Cited by 33 · see citing works
“01 when the AMPAR is located 200 nm away from the center of release (34).”
BackgroundEffects of Fast Presynaptic Noise in Attractor Neural Networks
Cortés, J. M., Torres, J. J., Marro, J., Garrido, P. L., & Kappen, H. J. (2006) · Neural Computation · doi:10.1162/089976606775623342 · Cited by 33 · see citing works
Wegner, W., Steffens, H., Gregor, C., Wolf, F., & Willig, K. I. (2022) · eLife · doi:10.7554/elife.73603 · Cited by 30 · see citing works
MacGillavry, H. D., & Hoogenraad, C. C. (2015) · Experimental Cell Research · doi:10.1016/j.yexcr.2015.02.024 · Cited by 31 · see citing works
“Because only a subset of AMPARs that is in the direct vicinity of the presynaptic site of release becomes activated, the local density of receptors apposing the release site is a critical determinant of synaptic strength [10 – 13].”
- 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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Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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