A circadian clock in hippocampus is regulated by interaction between oligophrenin- 1 and Rev-erbα

Pamela Valnegri (1) , Malik Khelfaoui (1) , Olivier Dorseuil (1) , Silvia Bassani (1) , Celine Lagneaux (1) , Antonella Gianfelice (1) , Roberta Benfante (1) , Jamel Chelly (1) , Pierre Billuart (1) , Carlo Sala (1) , Maria Passafaro (1)

1 Pharmacology

Oligophrenin-1 regulates dendritic spine morphology in brain. Mutations in the oligophrenin-1 gene cause intellectual disability. We report a new partner of oligophrenin-1, Rev-erbα: a nuclear receptor that represses the transcription of circadian oscillators. We show in mouse brain that oligophrenin-1 interacts with Rev-erbα, causing it to locate to dendrites, reducing its repressor activity, and protecting it from degradation. More importantly we demonstrate a circadian oscillator in hippocampus, involving the clock gene bmal1, modulated by Rev-erbα and requiring oligophrenin-1 for normal oscillation. We also show that synaptic activity induces Rev-erbα localization to dendrites and spines, a process mediated by AMPA receptor activation and requiring oligophrenin-1. Our data reveal new interactions between synaptic activity and circadian oscillators, and delineate a new means of communication between nucleus and synapse that may provide insight into normal plasticity and the etiology of intellectual disability.

Mots clés: Plasticity; Circadian Rhythms

Domaines: Neurosciences [q-bio.NC]

Pamela Valnegri, Malik Khelfaoui, Olivier Dorseuil, Silvia Bassani, Celine Lagneaux, et al.. A circadian clock in hippocampus is regulated by interaction between oligophrenin- 1 and Rev-erbα. Nature Neuroscience, 2011, ⟨10.1038/nn.2911⟩. ⟨hal-00674703⟩