We find that CCK+/CB1R+ IN axon targeting, synapse formation, and synapse function requires both glycosylation of α-Dag1 and interactions through the intracellular domain of β-Dag1, and that defects in synaptic structure and function is associated with increased seizure susceptibility in mouse models of dystroglycanopathy. Here, CCK is linked to neuromuscular disease caused by qualitative or quantitative defects of alpha-dystroglycan.