Mechanism and consequence of daily modulation of cortical parvalbumin-positive inhibitory neurons

Parvalbumin-positive (PV) neurons, the main class of inhibitory neurons in the neocortex, play critical roles in maintaining normal brain function and are implicated in a variety of brain disorders. Here we found that their function is modulated in a time- and sleep-dependent manner naturally during the day. We first show that PV-evoked inhibition is stronger by the end of the light (ZT12) compared to the end of dark (ZT0) cycle. In addition, both PV’s excitatory and inhibitory synaptic transmission slowly oscillate but in the opposite directions during the light/dark cycle. Whereas excitatory synapses are predominantly regulated by experience, inhibitory synapses are regulated by sleep. Mechanistically, we found that the daily regulation of PV’s inhibitory synapses is mediated by acetylcholine activating M1 receptors. Consistent with our ex vivo findings, we show in vivo that PV’s spontaneous activity display clear oscillation, which is opposite to that of the pyramidal neurons. Finally, we demonstrate that the daily changes in PV neural activity negatively correlate with the dLGN-evoked responses in V1, underscoring the physiological significance of PV’s daily regulation.