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Cortical synapses exhibit a marked short-term depression (STD) during sustained activation, largely due to the depletion of synaptic resources (vesicles). In most excitatory synapses the rate of replenishment of depleted vesicles is constant, determining an inverse relationship between the STD level and the activation rate, which theoretically, severely limits rate coding capabilities in these synapses. In contrast STD in inhibitory synapses made by parvalbumin-positive interneurons (PV-INs) is less affected by usage. We examined STD of the PV-IN to Pyramidal cell synapse in the mouse visual cortex, and found that in these synapses the recovery of depleted resources is not constant but increases linearly with the frequency of use. By combining modeling, dynamic clamp and optogenetics, we demonstrated that this dynamic regulation of recovery enables PV-INs to reduce pyramidal cell firing in a linear manner, which, theoretically, is crucial for controlling the gain of cortical visual responses.
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