SKUPIO, Urszula; WELTE, Julia; SERRAT, Roman; ERASO-PICHOT, Abel; JULIO-KALAJZIĆ, Francisca; GISQUET, Doriane; CANNICH, Astrid; DELCASSO, Sebastien; MATIAS, Isabelle; FUNDAZURI, Unai; POUVREAU, Sandrine; PAGANO ZOTTOLA, Antonio; LAVANCO, Gianluca; DRAGO, Filippo; RUIZ DE AZUA, Inigo; LUTZ, Beat; BELLOCCHIO, Luigi; BUSQUETS-GARCIA, Arnau; CHAOULOFF, Francis; MARSICANO, Giovanni

doi:10.1016/j.neuron.2023.04.001

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SKUPIO, Urszula
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]

WELTE, Julia
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]

SERRAT, Roman

Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]

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Neuron. 2023-06-21, vol. 111, n° 12, p. 1887-1897.e6

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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.< Leer menos

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Gaba

Consolidation

Corticosterone

Endocannabinoids

Hippocampus

Locus coeruleus

Mitochondrial cb(1) receptor

Mitochondrial calcium

Noradrenaline

Object recognition memory

Retrieval

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Mitochondrial cannabinoid receptors gate corticosterone impact on novel object recognition

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