title: An essential role of acetylcholine-glutamate synergy at habenular synapses in nicotine dependence.
abstract: A great deal of interest has been focused recently on the habenula and its critical role in aversion, negative-reward and drug dependence. Using a conditional mouse model of the ACh-synthesizing enzyme choline acetyltransferase (Chat), we report that local elimination of acetylcholine (ACh) in medial habenula (MHb) neurons alters glutamate corelease and presynaptic facilitation. Electron microscopy and immuno-isolation analyses revealed colocalization of ACh and glutamate vesicular transporters in synaptic vesicles (SVs) in the central IPN. Glutamate reuptake in SVs prepared from the IPN was increased by ACh, indicating vesicular synergy. Mice lacking CHAT in habenular neurons were insensitive to nicotine-conditioned reward and withdrawal. These data demonstrate that ACh controls the quantal size and release frequency of glutamate at habenular synapses, and suggest that the synergistic functions of ACh and glutamate may be generally important for modulation of cholinergic circuit function and behavior.
authors.affiliation: Molecular Neurobiology Group, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Frahm
authors.affiliation: Molecular Neurobiology Group, Max Delbrück Center for Molecular Medicine, Berlin, Germany.|Laboratory of Molecular Biology, The Rockefeller University, New York, United States.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Antolin-Fontes
authors.affiliation: Laboratory of Molecular Biology, The Rockefeller University, New York, United States.
authors.forename: Andreas
authors.initials: A
authors.lastname: Görlich
authors.affiliation: Institute for Integrative Neuroanatomy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Johannes-Friedrich
authors.initials: JF
authors.lastname: Zander
authors.affiliation: Institute for Integrative Neuroanatomy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Ahnert-Hilger
authors.affiliation: Molecular Neurobiology Group, Max Delbrück Center for Molecular Medicine, Berlin, Germany.|Laboratory of Molecular Biology, The Rockefeller University, New York, United States.
authors.forename: Ines
authors.initials: I
authors.lastname: Ibañez-Tallon
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D059329:Cholinergic Neurons / Q000502:physiology*; D003214:Conditioning, Classical; D018698:Glutamic Acid / Q000378:metabolism*; D019262:Habenula / Q000502:physiology*; D051379:Mice; D013569:Synapses / Q000187:drug effects*; D014029:Tobacco Use Disorder
chemical_list: D018698:Glutamic Acid; D000109:Acetylcholine
keywords: cholinergic; cotransmission; habenula; mouse; neuroscience; nicotine dependence; presynaptic facilitation; vesicular synergy