Spatiotemporally heterogeneous coordination of cholinergic and neocortical activity

Sweyta Lohani, Andrew H. Moberly, Hadas Benisty, Boris Landa, Miao Jing, Yulong Li, Michael J. Higley*, Jessica A. Cardin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1706-1713
Number of pages8
JournalNature Neuroscience
Issue number12
StatePublished - Dec 2022
Externally publishedYes


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