Year: 2026
Type: preprint
Abstract: In the central nervous system, synaptic transmission occurs through the probabilistic release of neurotransmitter vesicles following presynaptic action potentials (AP). Traditional models posit a single vesicle release event per AP, though experimental evidence indicates multivesicular release (MVR) may occur under some circumstances, greatly expanding the dynamic range and information content at single synapses. However, the quantal nature of synaptic transmission in the intact, waking brain is largely unknown. Here, we used two-photon imaging of iGluSnFR4f-expressing cortical axons and found that MVR dominates synaptic transmission at both layer 4 and layer 2/3 synapses, enhancing reliability and yielding non-binary signaling for single synaptic connections. Moreover, MVR in the presence of cholinergic modulation conveys behavioral state-dependent influence over synaptic potency. Overall, our findings demonstrate that MVR at central synapses in vivo contributes to the computational capacity of cortical circuits.
Authors: Paras A. Patel, Michael J. Higley
Institution: Yale University
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7223251057