Vangl2 in the Dentate Network Modulates Pattern Separation and Pattern Completion

Benjamin J.A. Robert (1) , Maïté M Moreau (1) , Steve dos Santos Carvalho (1) , Gael Barthet (2) , Claudia Racca (3) , Mehdi Bhouri (1) , Anne Quiedeville (1) , Maurice Garret (4) , Bénédicte Atchama (1) , Alice Shaam Al Abed (1) , Christelle Guette (1) , Deborah J Henderson (3) , Aline Desmedt (1) , Christophe Mulle (2) , Aline Marighetto (1) , Mireille Montcouquiol (1) , Nathalie Sans (1)

1 U1215 Inserm - UB - Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale
2 IINS - Interdisciplinary Institute for Neuroscience [Bordeaux]
3 Newcastle University [Newcastle]
4 INCIA - Institut de Neurosciences cognitives et intégratives d'Aquitaine

The organization of spatial information, including pattern completion and pattern separation processes, relies on the hippocampal circuits, yet the molecular and cellular mechanisms underlying these two processes are elusive. Here, we find that loss of Vangl2, a core PCP gene, results in opposite effects on pattern completion and pattern separation processes. Mechanistically, we show that Vangl2loss maintains young postmitotic granule cells in an immature state, providing increased cellular input for pattern separation. The genetic ablation of Vangl2disrupts granule cell morpho-functional maturation and further prevents CaMKII and GluA1 phosphorylation, disrupting the stabilization of AMPA receptors. As a functional consequence, LTP at lateral perforant path-GC synapses is impaired, leading to defects in pattern completion behavior. In conclusion, we show that Vangl2 exerts a bimodal regulation on young and mature GCs, and its disruption leads to an imbalance in hippocampus-dependent pattern completion and separation processes.

Mots clés: AMPA receptors; JNK; cognitive processes; computational function; granular cells; hippocampus; memory; noncanonical Wnt-PCP signaling; plasticity; polarity

Domaines: Neurobiologie

Benjamin J.A. Robert, Maïté M Moreau, Steve dos Santos Carvalho, Gael Barthet, Claudia Racca, et al.. Vangl2 in the Dentate Network Modulates Pattern Separation and Pattern Completion. Cell Reports, 2020, 31 (10), pp.107743. ⟨10.1016/j.celrep.2020.107743⟩. ⟨hal-03402580⟩