PT - JOURNAL ARTICLE AU - Lohani, Sweyta AU - Moberly, Andrew H. AU - Benisty, Hadas AU - Landa, Boris AU - Jing, Miao AU - Li, Yulong AU - Higley, Michael J. AU - Cardin, Jessica A. TI - Dual color mesoscopic imaging reveals spatiotemporally heterogeneous coordination of cholinergic and neocortical activity AID - 10.1101/2020.12.09.418632 DP - 2021 Jan 01 TA - bioRxiv PG - 2020.12.09.418632 4099 - http://biorxiv.org/content/early/2021/09/21/2020.12.09.418632.short 4100 - http://biorxiv.org/content/early/2021/09/21/2020.12.09.418632.full AB - Variation in an animal’s behavioral state is linked to fluctuations in brain activity and cognitive ability. In the neocortex, state-dependent control of circuit dynamics may reflect neuromodulatory influences including acetylcholine (ACh). While early literature suggested ACh exerts broad, homogeneous control over cortical function, recent evidence indicates potential anatomical and functional segregation of cholinergic signaling. Additionally, it is unclear whether states as defined by different behavioral markers reflect heterogeneous cholinergic and cortical network activity. We performed 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 increasing arousal, categorized by different motor behaviors, is associated with spatiotemporally dynamic patterns of cholinergic release 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.Competing Interest StatementThe authors have declared no competing interest.