摘要：SummaryAtypical cadherin Celsr3 is critical for brain embryonic development, and its role in the postnatal cerebellum remains unknown. UsingCelsr3-GFPmice, Celsr3 shows high expression in postnatal Purkinje cells (PCs). Mice with conditional knockout (cKO) ofCelsr3in 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) inCelsr3cKO mutants. Wnt5a perfusion enhances LTP formation, which could be occluded by cAMP agonist and diminished by cAMP antagonist in control, but not inCelsr3cKO orFzd3cKO cerebellar slices.Celsr3cKO 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.Graphical abstractDisplay OmittedHighlights•Celsr3cKO in postnatal PCs impairs mouse motor coordination and learning•Celsr3inactivation affects the maturation of PC dendrites and synapses•Celsr3 is required for the cerebellar LTP induction via the Wnt5a/cAMP signaling•Celsr3 regulates the cerebellar LTD induction through the mGluR1/PKCα pathwayDevelopmental neuroscience; Cognitive neuroscience
