Dynamic recovery from depression enables rate encoding in inhibitory synapses

Fast-spiking parvalbumin positive interneurons (PV-INs) are essential for controlling network firing and the gain of the cortical response to sensory stimulation. Crucial for these functions, PV-INs can sustain high frequency firing with no accommodation. However, PV-INs also exhibit short-term depression (STD) during sustained activation, which is largely due to the depletion of synaptic resources (vesicles). In most 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. 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.