Biophysical Society Conference | Estes Park 2023

Membrane Budding and Fusion

Tuesday Speaker Abstracts

FREQUENCY OF SPONTANEOUS VESICLE FUSION IS DETERMINED BY THE SIZE OF THE READILY RELEASABLE POOL AT INDIVIDUAL SYNAPSES

Amelia J Ralowicz ; Michael B Hoppa 1 ; 1 Dartmouth College, Department of Biology, Hanover, NH, USA

Synapses maintain two forms of neurotransmitter release to support communication in the brain, evoked and spontaneous. Evoked neurotransmitter release is triggered at a bouton by the invasion of an action potential. Even along a single axon, there is substantial variation in probability of evoked transmission (Pr) between individual boutons. The underlying basis for Pr is controlled by differences in the probability of vesicle fusion (Pv) and the number of vesicles available for release known as the readily-releasable pool (RRP). Spontaneous release (also known as a mini) is an important form of neurotransmission that occurs in the absence of action potentials. Because it cannot be triggered with electrical stimulation, much less is known about what controls spontaneous release. The process may be entirely stochastic or occur with highly heterogeneous frequencies at individual boutons. We utilized a new highly photostable fluorescent indicator of glutamate release (iGluSnFR3) to quantify both spontaneous and evoked release at individual glutamatergic boutons. We found that spontaneous release is quite heterogenous and cannot be explained as a stochastic process between individual boutons. We explored this heterogeneity in spontaneous release frequency in relation to evoked release in single boutons. Interestingly, we found that boutons with the highest rates of spontaneous release also displayed the largest evoked responses. Using a new optical method to measure RRP at individual boutons, we found that this heterogeneity was strongly correlated with the size of the RRP, but not related to Pv. We conclude that the RRP is a critical and dynamic aspect of synaptic strength that contributes to both evoked and spontaneous vesicle release. This finding has interesting implications for the purpose of spontaneous neurotransmission with regards to synaptic plasticity and stability.

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