Vesicular release probability sets the strength of individual Schaffer collateral synapses

Abstract

Information processing in the brain is controlled by quantal release of neurotransmitters, a tightly regulated process. From ultrastructural analysis, it is known that presynaptic boutons along single axons differ in the number of vesicles docked at the active zone. It is not clear whether the probability of these vesicles to get released (pves) is homogenous or also varies between individual boutons. Here, we optically measure evoked transmitter release at individual Schaffer collateral synapses at different calcium concentrations, using the genetically encoded glutamate sensor iGluSnFR. Fitting a binomial model to measured response amplitude distributions allowed us to extract the quantal parameters N, pves, and q. We find that Schaffer collateral boutons typically release single vesicles under low pves conditions and switch to multivesicular release in high calcium saline. The potency of individual boutons is highly correlated with their vesicular release probability while the number of releasable vesicles affects synaptic output only under high pves conditions.

BTSP, not STDP, Drives Shifts in Hippocampal Representations During Familiarization

“…Yu et al, 2006), but results were similar and we thus kept 100 inputs as our baseline for computation speed. Although 100 input place cells is not realistic, note that the distribution of synaptic weights with W max init = 85 pA fits well with the amplitude of CA1 EPSPs recorded in vivo or in vitro: EPSPs in vivo are 1.4 mV on average (Kowalski et al, 2016), EPSPs evoked by Schaffer stimulation in slices were ~2 mV on average (Bittner et al, 2017) which corresponds to 77pA with our LIF parameters (Fig S8), dual patch experiments between CA3 and CA1 pyramidal cells yield EPSCs of similar amplitudes (Dürst et al, 2022) and miniature EPSCs from a single synapse are 15 pA on average (0 to 30 pA range) (Forti et al, 1997). In Fig 2F and S5, PF in sd, Peak FR in and connectivity sd were varied systematically within a realistic range for CA3 but to cover both realistic and unrealistic PF properties for CA1.…”

Two forms of asynchronous release with distinctive spatiotemporal dynamics in central synapses

“…An alternative approach widely used previously to study asynchronous release relies on substitution of Ca 2+ for Sr 2+ (4 mM Sr 2+ application in 0.5 mM Ca 2+ ) ( Atluri and Regehr, 1998 ; Goda and Stevens, 1994 ; Rumpel and Behrends, 1999 ; Xu-Friedman and Regehr, 1999 ). Sr 2+ enhances asynchronous release approximately three- to fourfold due to its slower clearance rate and differential affinity to Syt1 in comparison to calcium ( Atluri and Regehr, 1998 ; Goda and Stevens, 1994 ; Rumpel and Behrends, 1999 ; Xu-Friedman and Regehr, 1999 ; Dürst et al, 2022 ). Indeed, we found that Sr 2+ application caused a significant reduction in synchronous release (p=0.0042, two-sample K-S test) and an increase in asynchronous release inside the AZ (p=0.028, two-sample K-S test; Figure 6—figure supplement 1A–C ).…”

Probabilities of evoked and spontaneous synaptic transmission at individual active zones: Lessons from Drosophila

“…The analysis of synaptic transmission at individual AZs will enable the investigation of the contribution of the synaptic machinery components to the stochastic properties of the release process, including its spatial and temporal heterogeneity and a possible interdependence of the release components and events across neighboring AZs, as well as within individual AZs. Notably, recent studies expressed GCaMP in dendritic spines to investigate the transmission heterogeneity at individual hippocampal synapses (Metzbower et al, 2019;Durst et al, 2022). These studies demonstrated that the method application is much broader than the Drosophila model, and that this approach will be instrumental for understanding the function of neuronal networks in the mammalian brain.…”

“…Notably, recent studies expressed GCaMP in dendritic spines to investigate the transmission heterogeneity at individual hippocampal synapses ( Metzbower et al, 2019 ; Durst et al, 2022 ). These studies demonstrated that the method application is much broader than the Drosophila model, and that this approach will be instrumental for understanding the function of neuronal networks in the mammalian brain.…”