Celsr3 is required for Purkinje cell maturation and regulates cerebellar postsynaptic plasticity.

Atypical cadherin Celsr3 is critical for brain embryonic development, and its role in the postnatal cerebellum remains unknown. Using mice, Celsr3 shows high expression in postnatal Purkinje cells (PCs). Mice with conditional knockout (cKO) of in postnatal PCs exhibit deficit in motor coordination and learning, atrophic PC dendrites, and decreased synapses. Whole-PC recording in cerebellar slices discloses a reduction frequency of mEPSC and defective postsynaptic plasticity (LTP and LTD) in cKO mutants. Wnt5a perfusion enhances LTP formation, which could be occluded by cAMP agonist and diminished by cAMP antagonist in control, but not in cKO or cKO cerebellar slices. cKO resulted in the failure of mGluR1 agonist-induced LTD and paired stimulation-induced PKCα overexpression in PC dendrites, and downregulation of mGluR1 expression compvared to controls. In conclusion, Celsr3 is required for PCs maturation and regulates postsynaptic LTP and LTD through Wnt5a/cAMP and mGluR1/PKCα signaling respectively.