Celsr3 is required in mouse hippocampal intrinsic wiring and spatial learning

ABSTRACT

Background The atypical cadherin Celsr3, which belongs to the core planar cell polarity group, orchestratesaxonal guidance and network wiring. Previous work using regional inactivation of Celsr3 in forebrain showedthat Celsr3 is widely involved in hippocampal maturation and connectivity. However, inactivation in the wholeforebrain does not provide sufficient specificity to address the function of Celsr3 in detail.Method We studied the Celsr3|Emx1 mouse mutant model, in which Celsr3 is selectively inactivated inhippocampal projection neurons, but not in entorhinal cortex, basal ganglia and interneurons.Result In that mutant, the hippocampal cytoarchitecture was almost normal. Inactivation of Celsr3 inprojection neurons perturbed intrinsic hippocampal wiring. Consistent with wiring defects, Celsr3|Emx1mutant mice showed impaired learning and memory, and were less anxiety-prone than control mice.Conclusion Celsr3|Emx1 mutant mice provide a simple way to study the consequences of defectivehippocampal wiring in absence of drastic structural anomalies.