Highlights d The excitation/inhibition (E/I) ratio is dynamic across the 24h day d Fluctuations in the E/I ratio depend on sleep/wake history d E/I ratio changes are circuit specific, not uniform across all synapses

Parvalbumin‐positive neurons (PVs) are the main class of inhibitory neurons in the mammalian central nervous system. By examining diurnal changes in synaptic and neuronal activity of PVs in the supragranular layer of the mouse primary visual cortex (V1), we found that both PV input and output are modulated in a time‐ and sleep‐dependent manner throughout the 24‐h day. We first show that PV‐evoked inhibition is stronger by the end of the light cycle (ZT12) relative to the end of the dark cycle (ZT0), which is in line with the lower inhibitory input of PV neurons at ZT12 than at ZT0. Interestingly, PV inhibitory and excitatory synaptic transmission slowly oscillate in opposite directions during the light/dark cycle. Although excitatory synapses are predominantly regulated by experience, inhibitory synapses are regulated by sleep, via acetylcholine activating M1 receptors. Consistent with synaptic regulation of PVs, we further show in vivo that spontaneous PV activity displays daily rhythm mainly determined by visual experience, which negatively correlates with the activity cycle of surrounding pyramidal neurons and the dorsal lateral geniculate nucleus‐evoked responses in V1. These findings underscore the physiological significance of PV's daily modulation.

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