LAUSR

Synapses contain a limited number of synaptic vesicles (SVs) that can be released in response to action potentials (APs). Therefore, sustaining synaptic transmission over a wide range of AP firing rates and timescales depends on both SV release and replenishment. Although actin dynamics impact synaptic transmission, how regulators of actin dynamics control SV release and replenishment remain unresolved. Rac1 is a regulator of actin signaling cascades that control synaptogenesis, neuronal development, and postsynaptic function, however, its presynaptic role in regulating synaptic transmission is unclear. To unravel the regulatory roles of presynaptic Rac1 in synaptic transmission, we ablated presynaptic Rac1 at the mature mouse calyx of Held. Presynaptic Rac1 deletion leads to increased synaptic strength due to increased SV release probability which results in faster SV replenishment and increased spontaneous SV release rates. Based on our data, we conclude that presynaptic Rac1 controls synaptic strength by regulating the intrinsic SV release probability through SV priming. Therefore, we propose that presynaptic Rac1 controls actin dynamics and acts as a key regulator of synaptic transmission and plasticity.