title: Coordinated Acetylcholine Release in Prefrontal Cortex and Hippocampus Is Associated with Arousal and Reward on Distinct Timescales.
abstract: 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.
authors.affiliation: Lilly Centre for Cognitive Neuroscience, Eli Lilly and Company Ltd., Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK; Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Leonor M
authors.initials: LM
authors.lastname: Teles-Grilo Ruivo
authors.affiliation: Department of Chemistry, Maynooth University, Co. Kildare, Ireland.
authors.forename: Keeley L
authors.initials: KL
authors.lastname: Baker
authors.affiliation: Lilly Centre for Cognitive Neuroscience, Eli Lilly and Company Ltd., Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Conway
authors.affiliation: Lilly Centre for Cognitive Neuroscience, Eli Lilly and Company Ltd., Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Kinsley
authors.affiliation: Lilly Centre for Cognitive Neuroscience, Eli Lilly and Company Ltd., Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK.
authors.forename: Gary
authors.initials: G
authors.lastname: Gilmour
authors.affiliation: Lilly Centre for Cognitive Neuroscience, Eli Lilly and Company Ltd., Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK.
authors.forename: Keith G
authors.initials: KG
authors.lastname: Phillips
authors.affiliation: Lilly Centre for Cognitive Neuroscience, Eli Lilly and Company Ltd., Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK.
authors.forename: John T R
authors.initials: JTR
authors.lastname: Isaac
authors.affiliation: Department of Chemistry, Maynooth University, Co. Kildare, Ireland. Electronic address: john.lowry@nuim.ie.
authors.forename: John P
authors.initials: JP
authors.lastname: Lowry
authors.affiliation: Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol BS8 1TD, UK. Electronic address: jack.mellor@bristol.ac.uk.
authors.forename: Jack R
authors.initials: JR
authors.lastname: Mellor
mesh_terms: D000109:Acetylcholine / Q000032:analysis* / Q000378:metabolism; D000818:Animals; D001143:Arousal; D001522:Behavior, Animal; D015374:Biosensing Techniques; D055664:Electrochemical Techniques; D004567:Electrodes, Implanted; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D008124:Locomotion; D008297:Male; D018782:Maze Learning; D008570:Memory, Short-Term; D051379:Mice; D008810:Mice, Inbred C57BL; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology; D012201:Reward; D012895:Sleep, REM; D014851:Wakefulness
chemical_list: D000109:Acetylcholine
keywords: acetylcholine; biosensor; hippocampus; prefrontal cortex