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Updated: Jan 28, 2026

Optogenetic Manipulation of Neural Circuits During Monitoring Sleep/wakefulness States in Mice
Published on: June 19, 2019
Cholinergic modulation of hippocampal calcium activity across the sleep-wake cycle
Heng Zhou1, Kevin R Neville1, Nitsan Goldstein1
1MasGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Charlestown, United States.
Abstract:
Calcium is a critical second messenger in neurons that contributes to learning and memory, but how the coordination of action potentials of neuronal ensembles with the hippocampal local field potential (LFP) is reflected in dynamic calcium activity remains unclear. Here, we recorded hippocampal calcium activity with endoscopic imaging of the genetically encoded fluorophore GCaMP6 with concomitant LFP in freely behaving mice. Dynamic calcium activity was greater in exploratory behavior and REM sleep than in quiet wakefulness and slow wave sleep, behavioral states that differ with respect to theta and septal cholinergic activity, and modulated at sharp wave ripples (SWRs). Chemogenetic activation of septal cholinergic neurons expressing the excitatory hM3Dq DREADD increased calcium activity and reduced SWRs. Furthermore, inhibition of muscarinic acetylcholine receptors (mAChRs) reduced calcium activity while increasing SWRs. These results demonstrate that hippocampal dynamic calcium activity depends on behavioral and theta state as well as endogenous mAChR activation.
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