title: Habenular CB1 Receptors Control the Expression of Aversive Memories.
abstract: Expression of aversive memories is key for survival, but the underlying brain mechanisms are not fully understood. Medial habenular (MHb) axons corelease glutamate and acetylcholine onto target postsynaptic interpeduncular (IPN) neurons, but their role in aversive memories has not been addressed so far. We found that cannabinoid type 1 receptors (CB1R), key regulators of aversive responses, are present at presynaptic terminals of MHb neurons in the IPN. Conditional deletion of CB1R from MHb neurons reduces fear-conditioned freezing and abolishes conditioned odor aversion in mice, without affecting neutral or appetitively motivated memories. Interestingly, local inhibition of nicotinic, but not glutamatergic receptors in the target region IPN before retrieval, rescues these phenotypes. Finally, optogenetic electrophysiological recordings of MHb-to-IPN circuitry revealed that blockade of CB1R specifically enhances cholinergic, but not glutamatergic, neurotransmission. Thus, presynaptic CB1R control expression of aversive memories by selectively modulating cholinergic transmission at MHb synapses in the IPN.
authors.affiliation: INSERM, U862 NeuroCentre Magendie, Group Endocannabinoids and Neuroadaptation, Bordeaux 33077, France; University of Bordeaux, Bordeaux 33077, France.
authors.forename: Edgar
authors.initials: E
authors.lastname: Soria-Gómez
authors.affiliation: INSERM, U862 NeuroCentre Magendie, Group Endocannabinoids and Neuroadaptation, Bordeaux 33077, France; University of Bordeaux, Bordeaux 33077, France.
authors.forename: Arnau
authors.initials: A
authors.lastname: Busquets-Garcia
authors.affiliation: National Institute of Biological Sciences, Beijing 100875, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Hu
authors.affiliation: INSERM, U862 NeuroCentre Magendie, Group Endocannabinoids and Neuroadaptation, Bordeaux 33077, France; University of Bordeaux, Bordeaux 33077, France.
authors.forename: Amine
authors.initials: A
authors.lastname: Mehidi
authors.affiliation: INSERM, U862 NeuroCentre Magendie, Group Endocannabinoids and Neuroadaptation, Bordeaux 33077, France; University of Bordeaux, Bordeaux 33077, France.
authors.forename: Astrid
authors.initials: A
authors.lastname: Cannich
authors.affiliation: INSERM, U862 NeuroCentre Magendie, Group Endocannabinoids and Neuroadaptation, Bordeaux 33077, France; University of Bordeaux, Bordeaux 33077, France.
authors.forename: Liza
authors.initials: L
authors.lastname: Roux
authors.affiliation: INSERM, U862 NeuroCentre Magendie, Group Endocannabinoids and Neuroadaptation, Bordeaux 33077, France; University of Bordeaux, Bordeaux 33077, France.
authors.forename: Ines
authors.initials: I
authors.lastname: Louit
authors.affiliation: INSERM, U862 NeuroCentre Magendie, Group Endocannabinoids and Neuroadaptation, Bordeaux 33077, France; University of Bordeaux, Bordeaux 33077, France.
authors.forename: Lucille
authors.initials: L
authors.lastname: Alonso
authors.affiliation: INSERM, U862 NeuroCentre Magendie, Group Endocannabinoids and Neuroadaptation, Bordeaux 33077, France; University of Bordeaux, Bordeaux 33077, France.
authors.forename: Theresa
authors.initials: T
authors.lastname: Wiesner
authors.affiliation: University of Bordeaux, Bordeaux 33077, France; CNRS, UMR 5297 Interdisciplinary Institute for Neuroscience, Bordeaux 33077, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Georges
authors.affiliation: INSERM, U862 NeuroCentre Magendie, Group Endocannabinoids and Neuroadaptation, Bordeaux 33077, France; University of Bordeaux, Bordeaux 33077, France.
authors.forename: Danièle
authors.initials: D
authors.lastname: Verrier
authors.affiliation: INSERM, U862 NeuroCentre Magendie, Group Endocannabinoids and Neuroadaptation, Bordeaux 33077, France; University of Bordeaux, Bordeaux 33077, France.
authors.forename: Peggy
authors.initials: P
authors.lastname: Vincent
authors.affiliation: University of Bordeaux, Bordeaux 33077, France; INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux 33077, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Ferreira
authors.affiliation: National Institute of Biological Sciences, Beijing 100875, China.
authors.forename: Minmin
authors.initials: M
authors.lastname: Luo
authors.affiliation: INSERM, U862 NeuroCentre Magendie, Group Endocannabinoids and Neuroadaptation, Bordeaux 33077, France; University of Bordeaux, Bordeaux 33077, France. Electronic address: giovanni.marsicano@inserm.fr.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marsicano
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D005239:Fear / Q000502:physiology* / Q000523:psychology; D019262:Habenula / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency / Q000502:physiology*
chemical_list: D043884:Receptor, Cannabinoid, CB1