Cholinergic modulation of hippocampal calcium activity across the sleep-wake cycle
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.
Imaging data has been deposited into Dryad, and is available at doi:10.5061/dryad.8ct101p
Data from: Cholinergic modulation of hippocampal calcium activity across the sleep-wake cycleDryad Digital Repository, doi:10.5061/dryad.8ct101p.
Article and author information
National Institute on Aging (1R01 AG054551)
- Stephen N Gomperts
- Bradley T Hyman
- Stephen N Gomperts
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to an approved institutional animal care and use committee (IACUC) protocol (2012N000206) of the Massachusetts General Hospital. All surgery was performed under isoflurane anesthesia, and every effort was made to minimize suffering.
- Laura Colgin, The University of Texas at Austin, United States
- Received: July 2, 2018
- Accepted: February 15, 2019
- Accepted Manuscript published: March 7, 2019 (version 1)
- Version of Record published: March 26, 2019 (version 2)
© 2019, Zhou et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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