title: Orexin-driven GAD65 network of the lateral hypothalamus sets physical activity in mice.
abstract: Damage to the lateral hypothalamus (LH) causes profound physical inactivity in mammals. Several molecularly distinct types of LH neurons have been identified, including orexin cells and glutamic acid decarboxylase 65 (GAD65) cells, but their interplay in orchestrating physical activity is not fully understood. Here, using optogenetic circuit analysis and cell type-specific deep-brain recordings in behaving mice, we show that orexin cell activation rapidly recruits GAD65LHneurons. We demonstrate that internally initiated GAD65LHcell bursts precede and accompany spontaneous running bouts, that selective chemogenetic silencing of natural GAD65LHcell activity depresses voluntary locomotion, and that GAD65LHcell overactivation leads to hyperlocomotion. These results thus identify a molecularly distinct, orexin-activated LH submodule that governs physical activity in mice.
authors.affiliation: The Francis Crick Institute, London NW1 1AT, United Kingdom.
authors.forename: Christin
authors.initials: C
authors.lastname: Kosse
authors.affiliation: Centre for Experimental Neurology, Inselspital University Hospital, Bern 3010, Switzerland.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schöne
authors.affiliation: The Francis Crick Institute, London NW1 1AT, United Kingdom.
authors.forename: Edward
authors.initials: E
authors.lastname: Bracey
authors.affiliation: The Francis Crick Institute, London NW1 1AT, United Kingdom; d.burdakov@oxon.org.|Department of Developmental Neurobiology, King's College London, London WC2R 2LS, United Kingdom.
authors.forename: Denis
authors.initials: D
authors.lastname: Burdakov
mesh_terms: D000818:Animals; D004562:Electrocardiography; D018014:Gene Transfer Techniques; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism*; D007026:Hypothalamic Area, Lateral / Q000502:physiology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000502:physiology*; D000068797:Orexins / Q000502:physiology*
chemical_list: D000068797:Orexins; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2
keywords: GAD65; hypocretin; hypothalamus; locomotion; orexin; stress