• Celsr3 knockout in Purkinje cells causes ataxia-like behavior and synaptic deficits, including impaired mEPSCs and LTP.
• Forskolin, a cAMP activator, ameliorates ataxia-like behavior and restores synaptic function in Celsr3 cKO mice.
• The therapeutic effects of forskolin are mediated via the cAMP/Epac pathway, not PKA, as shown by antagonist studies.
• Forskolin represents a potential therapeutic agent for inherited cerebellar ataxias involving synaptic dysfunction.