Vangl2 in the Dentate Network Modulates Pattern Separation and Pattern Completion

• Published in: Cell reports (Cambridge) Vol. 31; no. 10; p. 107743
• Main Authors: Robert, Benjamin J.A., Moreau, Maïté M., Dos Santos Carvalho, Steve, Barthet, Gael, Racca, Claudia, Bhouri, Mehdi, Quiedeville, Anne, Garret, Maurice, Atchama, Bénédicte, Al Abed, Alice Shaam, Guette, Christelle, Henderson, Deborah J., Desmedt, Aline, Mulle, Christophe, Marighetto, Aline, Montcouquiol, Mireille, Sans, Nathalie
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.06.2020; Cell Press
• Subjects: AMPA receptors; Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism; Cell Polarity - physiology; cognitive processes; computational function; Dentate Gyrus - cytology; Dentate Gyrus - metabolism; granular cells; hippocampus; JNK; Life Sciences; Male; memory; Mice; Mice, Inbred C57BL; Mice, Knockout; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurons and Cognition; noncanonical Wnt-PCP signaling; Phosphorylation; plasticity; polarity; Receptors, AMPA - metabolism; memory; hippocampus; computational function; JNK; cognitive processes; noncanonical Wnt-PCP signaling; plasticity; AMPA receptors; granular cells; polarity
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.107743

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. [Display omitted] •Vangl2-dependent PCP signaling controls granule cell maturation and network integration•Vangl2 stabilizes GluA1-containing receptors at the surface of dendritic spines•Granule cells require Vangl2-dependent signaling to elicit LTP•Vangl2 loss has opposite functional effects on pattern completion/separation processes Robert et al. show that Vangl2 is required for proper granule cell maturation, thus influencing network integration, and that Vangl2 absence in the hippocampus inversely modulates pattern completion and pattern separation. These findings demonstrate inter-independence of the two processes via Vangl2 control of the dentate gyrus network.