Habenular CB1 Receptors Control the Expression of Aversive Memories.
Neuron. 2015-10-01; 88(2): 306-313
DOI: 10.1016/j.neuron.2015.08.035
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1. Neuron. 2015 Oct 21;88(2):306-13. doi: 10.1016/j.neuron.2015.08.035. Epub 2015
Sep 24.
Habenular CB1 Receptors Control the Expression of Aversive Memories.
Soria-Gómez E(1), Busquets-Garcia A(1), Hu F(2), Mehidi A(1), Cannich A(1), Roux
L(1), Louit I(1), Alonso L(1), Wiesner T(1), Georges F(3), Verrier D(1), Vincent
P(1), Ferreira G(4), Luo M(2), Marsicano G(5).
Author information:
(1)INSERM, U862 NeuroCentre Magendie, Group Endocannabinoids and Neuroadaptation,
Bordeaux 33077, France; University of Bordeaux, Bordeaux 33077, France.
(2)National Institute of Biological Sciences, Beijing 100875, China.
(3)University of Bordeaux, Bordeaux 33077, France; CNRS, UMR 5297
Interdisciplinary Institute for Neuroscience, Bordeaux 33077, France.
(4)University of Bordeaux, Bordeaux 33077, France; INRA, Nutrition et
Neurobiologie Intégrée, UMR 1286, Bordeaux 33077, France.
(5)INSERM, U862 NeuroCentre Magendie, Group Endocannabinoids and Neuroadaptation,
Bordeaux 33077, France; University of Bordeaux, Bordeaux 33077, France.
Electronic address: .
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.
Copyright © 2015 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.neuron.2015.08.035
PMID: 26412490 [Indexed for MEDLINE]