Cholinergic neuron

Psychology

Neuroscience

Cholinergic

Oligodendrocyte

Neocortex

Myelin

Neuroscientist

Cholinergic system

Central nervous system

Nature Neuroscience

Variation in an animal’s behavioral state is linked to fluctuations in brain activity and cognitive ability. In the neocortex, state-dependent circuit dynamics may reflect neuromodulatory influences such as that of acetylcholine (ACh). Although early literature suggested that ACh exerts broad, homogeneous control over cortical function, recent evidence indicates potential anatomical and functional segregation of cholinergic signaling. In addition, it is unclear whether states as defined by different behavioral markers reflect heterogeneous cholinergic and cortical network activity. Here, we perform simultaneous, dual-color mesoscopic imaging of both ACh and calcium across the neocortex of awake mice to investigate their relationships with behavioral variables. We find that higher arousal, categorized by different motor behaviors, is associated with spatiotemporally dynamic patterns of cholinergic modulation and enhanced large-scale network correlations. Overall, our findings demonstrate that ACh provides a highly dynamic and spatially heterogeneous signal that links fluctuations in behavior to functional reorganization of cortical networks. Using dual-color mesoscopic imaging in the neocortex of awake mice, the authors show that cholinergic release and neuronal activity exhibit distinct spatiotemporal patterns that are differentially linked to spontaneous fluctuations in behavioral state.

Spatiotemporally heterogeneous coordination of cholinergic and neocortical activity