Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (UMR5287)

Aquitaine Institute for Cognitive and Integrative Neuroscience



INCIA - UMR 5287- CNRS
Université de Bordeaux

Zone nord Bat 2 2ème étage
146, rue Léo Saignat
33076 Bordeaux cedex
France

Téléphone 05.57.57.15.51
Télécopie 05.56.90.14.21

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CNRS Ecole Pratique des Hautes Etudes Université de Bordeaux

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Home > Latest publications

Inhibitory neurotransmission drives endocannabinoid degradation to promote memory consolidation.

Christophe J. Dubois1, 2, Jessica Fawcett-Patel1, , Paul A. Katzman1 and Siqiong June Liu1, 3, *

by Loïc Grattier - published on

Nat Commun 11, (2020) https://doi.org/10.1038/s41467-020-20121-3

1 Department of Cell Biology and Anatomy, LSU Health Sciences Center, New Orleans, LA 70112 USA.
2 Present address: Univ. Bordeaux, CNRS, EPHE, INCIA, UMR 5287, F-33000 Bordeaux, France.
3 Southeast Louisiana VA Healthcare System, New Orleans, Louisiana 70119, USA.
Co-first author

Endocannabinoids regulate many aspects of brain function by suppressing synaptic transmission via an on-demand release and activation of endocannabinoid receptors. A key regulator is the degradation process because this controls the temporal profile of endocannabinoid action. A fundamental question is whether endocannabinoid degradation plays a house-keeping role or is dynamically regulated by neuronal activity and thus actively participates in learning. Here we show that fear conditioning accelerates the degradation of endocannabinoids in the cerebellar cortex and this effect is driven by a learning-induced lasting increase in GABA release. Pharmacogenetic activation of cerebellar Purkinje cells after fear conditioning enhanced tonic endocannabinoid signaling and impaired cued memory retention via a CB1 receptor-mediated pathway. Therefore a learning-induced increase in GABA release accelerates 2-AG degradation in the cerebellum and drives the consolidation of fear memory. This novel form of degradation-dependent plasticity remodels synaptic integration and information processing within a neuronal circuit.

View online : https://www.nature.com/articles/s41...