Estimating the Readily-Releasable Vesicle Pool Size at Synaptic Connections in the Neocortex

Abstract

Previous studies based on the ‘Quantal Model’ for synaptic transmission suggest that neurotransmitter release is mediated by a single release site at individual synaptic contacts in the neocortex. However, recent studies seem to contradict this hypothesis and indicate that multi-vesicular release (MVR) could better explain the synaptic response variability observed in vitro. In this study we present a novel method to estimate the number of release sites per synapse, also known as the size of the readily releasable pool (NRRP), from paired whole-cell recordings of connections between layer 5 thick tufted pyramidal cell (L5_TTPC) in the juvenile rat somatosensory cortex. Our approach extends the work of Loebel et al. (2009) by leveraging a recently published data-driven biophysical model of neocortical tissue. Using this approach, we estimated NRRP to be between two to three for synaptic connections between L5_TTPCs. To constrain NRRP values for other connections in the microcircuit, we developed and validated a generalization approach using published data on the coefficient of variation (CV) of the amplitudes of post-synaptic potentials (PSPs) from literature and comparing them against in silico experiments. Our study predicts that transmitter release at synaptic connections in the neocortex could be mediated by MVR and provides a data-driven approach to constrain the MVR model parameters in the microcircuit.

Ultrafast Simulation of Large-Scale Neocortical Microcircuitry with Biophysically Realistic Neurons

“…Many important advancements have recently been made in the development of detailed, large-scale network simulations, however, the bottleneck continues to be slow simulation runtimes. Consequently, network simulations can be carried out only a few times (but see 103 ), hindering imperative network construction steps, such as parameter space optimization. To establish whether this bottleneck could be remedied by the drastic runtime acceleration with ANNs, we explored the influence of several network parameters on circuit behavior in a model of Rett syndrome.…”

A calcium-based plasticity model predicts long-term potentiation and depression in the neocortex

“…the dendrites, number of synapses per connection and vesicle release dynamics Reimann et al, 2015;Barros-Zulaica et al, 2019).…”

“…Vesicle release is described using a stochastic version of the canonical Tsodyks-Markram (TM) model with multi-vesicular release (MVR) (Tsodyks and Markram, 1997;Ramaswamy et al, 2012;Markram et al, 2015;Ramaswamy et al, 2015;Barros-Zulaica et al, 2019). It is effectively analogous to the traditional binomial model of vesicle release B(N RRP , U (t)), where N RRP is the number of vesicles available at any given moment in the RRP and is and U (t) is the dynamical release probability of the TM formalism:…”

Unveiling the Synaptic Function and Structure Using Paired Recordings From Synaptically Coupled Neurons

“…In contrast, synaptic connections between layer 4 excitatory neurons exhibit either UVR in the primary visual cortex or MVR in the primary somatosensory cortex of mice (Huang et al, 2010). Synaptic connections between layer 5B pyramidal cells also exhibit MVR in the developing and adult somatosensory cortex of rats (Rollenhagen et al, 2018;Barros-Zulaica et al, 2019). Depending on the species, synaptic connections between pyramidal cells and interneurons exhibit either UVR in the rat neocortex or MVR in the human neocortex (Molnar et al, 2016).…”