Mitochondrial cannabinoid receptors gate corticosterone impact on novel object recognition

Urszula Skupio, Julia Welte, Roman Serrat, Abel Eraso-Pichot, Francisca Julio-Kalajzić, Doriane Gisquet, Astrid Cannich, Sebastien Delcasso, Isabelle Matias, Unai B. Fundazuri, Sandrine Pouvreau, Antonio C. Pagano Zottola, Gianluca Lavanco, Filippo Drago, Inigo Ruiz de Azua, Beat Lutz, Luigi Bellocchio, Arnau Busquets-Garcia, Francis Chaouloff, Giovanni Marsicano
Neuron. 2023-04-01; :
DOI: 10.1016/j.neuron.2023.04.001

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Skupio U(1), Welte J(1), Serrat R(1), Eraso-Pichot A(1), Julio-Kalajzić F(1), Gisquet D(1), Cannich A(1), Delcasso S(2), Matias I(1), Fundazuri UB(1),
Pouvreau S(1), Pagano Zottola AC(3), Lavanco G(1), Drago F(4), Ruiz de Azua I(5), Lutz B(5), Bellocchio L(1), Busquets-Garcia A(6), Chaouloff F(1),
Marsicano G(7).

Author information:
(1)INSERM, U1215 NeuroCentre Magendie, Bordeaux 33077, France; University of
Bordeaux, Bordeaux 33077, France.
(2)Aquineuro, Begles 33130, France.
(3)INSERM, U1215 NeuroCentre Magendie, Bordeaux 33077, France; University of
Bordeaux, Bordeaux 33077, France; Institute for Cellular Biochemistry and
Genetics, UMR 5095, Bordeaux 33077, France.
(4)Department of Clinical and Molecular Biomedicine, Section of Pharmacology and
Biochemistry, University of Catania, Catania, Italy.
(5)Institute of Physiological Chemistry, University Medical Center, Mainz 55131
Germany; Leibniz Institute for Resilience Research (LIR), Mainz 55122, Germany.
(6)Cell-Type Mechanisms in Normal and Pathological Behavior Research Group,
Neuroscience Program, IMIM Hospital del Mar Medical Research Institute,
Barcelona 08003, Spain.
(7)INSERM, U1215 NeuroCentre Magendie, Bordeaux 33077, France; University of
Bordeaux, Bordeaux 33077, France. Electronic address:

Corticosteroid-mediated stress responses require the activation of complex brain
circuits involving mitochondrial activity, but the underlying cellular and
molecular mechanisms are scantly known. The endocannabinoid system is implicated
in stress coping, and it can directly regulate brain mitochondrial functions via
type 1 cannabinoid (CB1) receptors associated with mitochondrial membranes
(mtCB1). In this study, we show that the impairing effect of corticosterone in
the novel object recognition (NOR) task in mice requires mtCB1 receptors and the
regulation of mitochondrial calcium levels in neurons. Different brain circuits
are modulated by this mechanism to mediate the impact of corticosterone during
specific phases of the task. Thus, whereas corticosterone recruits mtCB1
receptors in noradrenergic neurons to impair NOR consolidation, mtCB1 receptors
in local hippocampal GABAergic interneurons are required to inhibit NOR
retrieval. These data reveal unforeseen mechanisms mediating the effects of
corticosteroids during different phases of NOR, involving mitochondrial calcium
alterations in different brain circuits.

Copyright © 2023 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.neuron.2023.04.001
PMID: 37098353

Conflict of interest statement: Declaration of interests The authors declare no
competing interests.

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