Acetylcholine mediates behavioral state-dependent modulation of spontaneous activity in the developing mouse visual cortex
Synchronized and desynchronized patterns of spontaneous activity during brain development prepare cortical circuits such as the visual cortex for processing external sensory information. Yet the neuromodulatory mechanisms that regulate these early activity patterns remain poorly understood. One such neuromodulator is acetylcholine, which tracks behavioral states and modulates visual cortical activity in adults, but whose function in the developing cortex is largely unexplored. Here, we combined in vivo imaging of genetically encoded acetylcholine and calcium sensors with movement recordings to characterize the relationship between cholinergic dynamics, neuronal activity, and behavioral states in the mouse visual cortex during the second postnatal week, before eye opening. We found that acetylcholine release in the primary visual cortex (V1) closely tracked body movements but was not evoked by visual stimulation alone. Periods of elevated acetylcholine were associated with reduced pairwise neuronal correlations, longer network events with greater temporal jitter, and a transient reduction in mean V1 activity. Chemogenetic inhibition of basal forebrain cholinergic neurons increased the internal synchrony of network events and partially reversed the movement-associated reduction in V1 activity, identifying basal forebrain input as a source of this cholinergic modulation. These findings establish acetylcholine as a state-dependent regulator of spontaneous activity in the developing visual cortex before visual experience begins.