Vangl2 in the Dentate Network Modulates Pattern Separation and Pattern Completion
Cell Reports. 2020-06-01; 31(10): 107743
DOI: 10.1016/j.celrep.2020.107743
Lire sur PubMed
Robert BJA(1), Moreau MM(1), Dos Santos Carvalho S(1), Barthet G(2), Racca C(3), Bhouri M(1), Quiedeville A(1), Garret M(4), Atchama B(1), Al Abed AS(1), Guette C(1), Henderson DJ(5), Desmedt A(1), Mulle C(2), Marighetto A(1), Montcouquiol M(6), Sans N(7).
Author information:
(1)INSERM, Neurocentre Magendie, U1215, 33000 Bordeaux, France; Université Bordeaux, Neurocentre Magendie, 33000 Bordeaux, France.
(2)CNRS, IINS, UMR 5297, 33000 Bordeaux, France; Université Bordeaux, IINS, 33000 Bordeaux, France.
(3)Biosciences Institute, Newcastle University, Medical School, Newcastle upon Tyne, NE2 4HH, UK.
(4)CNRS, INCIA, 33000 Bordeaux, France; Université Bordeaux, INCIA, 30000 Bordeaux, France.
(5)Biosciences Institute, Newcastle University, Centre for Life, Newcastle upon Tyne, NE1 4EP, UK.
(6)INSERM, Neurocentre Magendie, U1215, 33000 Bordeaux, France; Université Bordeaux, Neurocentre Magendie, 33000 Bordeaux, France. Electronic address: .
(7)INSERM, Neurocentre Magendie, U1215, 33000 Bordeaux, France; Université Bordeaux, Neurocentre Magendie, 33000 Bordeaux, France. Electronic address: .
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 Vangl2 loss maintains young postmitotic granule cells in an immature state, providing increased cellular input for pattern separation. The genetic ablation of Vangl2 disrupts 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.