Coordinated Acetylcholine Release in Prefrontal Cortex and Hippocampus Is Associated with Arousal and Reward on Distinct Timescales

Publication date: 24 January 2017
Source:Cell Reports, Volume 18, Issue 4
Author(s): Leonor M. Teles-Grilo Ruivo, Keeley L. Baker, Michael W. Conway, Peter J. Kinsley, Gary Gilmour, Keith G. Phillips, John T.R. Isaac, John P. Lowry, Jack R. Mellor
Cholinergic neurotransmission throughout the neocortex and hippocampus regulates arousal, learning, and attention. However, owing to the poorly characterized timing and location of acetylcholine release, its detailed behavioral functions remain unclear. Using electrochemical biosensors chronically implanted in mice, we made continuous measurements of the spatiotemporal dynamics of acetylcholine release across multiple behavioral states. We found that tonic levels of acetylcholine release were coordinated between the prefrontal cortex and hippocampus and maximal during training on a rewarded working memory task. Tonic release also increased during REM sleep but was contingent on subsequent wakefulness. In contrast, coordinated phasic acetylcholine release occurred only during the memory task and was strongly localized to reward delivery areas without being contingent on trial outcome. These results show that coordinated acetylcholine release between the prefrontal cortex and hippocampus is associated with reward and arousal on distinct timescales, providing dual mechanisms to support learned behavior acquisition during cognitive task performance.

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Teaser

In this study, Teles-Grilo Ruivo et al. use biosensors to simultaneously measure the release profiles of the neuromodulator acetylcholine in the prefrontal cortex and hippocampus of mice. They find that release on both tonic and phasic timescales is remarkably coordinated between brain regions and dependent on behavioral state.


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