Differential control of presynaptic efficacy by postsynaptic N-cadherin and β-catenin

N-cadherin is a homophilic adhesion protein that remains expressed at mature excitatory synapses beyond its developmental role in synapse formation. We have investigated the transsynaptic activity of N-cadherin in regulating synapse function in rodent cultured hippocampal neurons using optical methods and electrophysiology. Interfering with N-cadherin in postsynaptic neurons reduces basal release probability (p(r)) at inputs to the neuron, and this transsynaptic impairment of release accompanies impaired vesicle endocytosis. Moreover, the loss of GluA2, which decreases p(r) by itself, occludes the effect of interfering with postsynaptic N-cadherin. The loss of postsynaptic N-cadherin activity, however, does not affect the compensatory upregulation of p(r) induced by activity silencing, while postsynaptic β-catenin deletion blocks this presynaptic homeostatic adaptation. Our findings suggest that postsynaptic N-cadherin plays a role in linking basal pre- and postsynaptic strengths to control the level of p(r) offset while the gain adjustment of p(r) requires a distinct transsynaptic pathway involving β-catenin.