4.4 Article

Properties of quantal transmission at CA1 synapses

Journal

JOURNAL OF NEUROPHYSIOLOGY
Volume 92, Issue 4, Pages 2456-2467

Publisher

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/jn.00258.2004

Keywords

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Funding

  1. NINDS NIH HHS [R01-NS-27337, R01-NS-35083] Funding Source: Medline

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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 mu s) than previously thought. The simulations show that initial channel opening is driven by a brief (<100 mus) glutamate spike near the site of vesicle fusion, producing a hotspot of channel activation (diameter: similar to250 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 similar to10 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 the existence of these narrow peaks, which indicate that the variation of quantal amplitude is small (CV<0.2) with the highly variable amplitude of miniature EPSCs (mEPSCs; CV similar to 0.6). According to one theory, mEPSC variability arises from variation in vesicle glutamate content. However, both our modeling results and recent experimental results indicate that this view cannot account for the observed rise time/amplitude correlation of mEPSCs. In contrast, this correlation and the high mEPSC variability can be accounted for if some mEPSCs are generated by two or more vesicles released with small temporal jitter. We conclude that a broad range of results can be accounted for by simple principles: quantal amplitude (similar to 10 pA) is stereotyped, some mEPSCs are multivesicular at moderate and large synapses, and evoked responses are generated by quasi-linear summation of multiple quanta.

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