Multiquantal transmission supports dynamic synaptic strength in vivo

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.