Differential control of presynaptic efficacy by postsynaptic N-cadherin and β-catenin
Nat Neurosci. 2011-12-04; 15(1): 81-89
DOI: 10.1038/nn.2995
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N-cadherin is a homophilic adhesion protein that remains expressed at mature
excitatory synapses beyond its developmental role in synapse formation. We
investigated the trans-synaptic 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 reduced
basal release probability (p(r)) at inputs to the neuron, and this trans-synaptic
impairment of release accompanied impaired vesicle endocytosis. Moreover, loss of
the GluA2 AMPA-type glutamate receptor subunit, which decreased p(r) by itself,
occluded the interference with postsynaptic N-cadherin. The loss of postsynaptic
N-cadherin activity, however, did not affect the compensatory upregulation of
p(r) induced by chronic activity silencing, whereas postsynaptic β-catenin
deletion blocked this presynaptic homeostatic adaptation. Our findings suggest
that postsynaptic N-cadherin helps link basal pre- and postsynaptic strengths to
control the p(r) offset, whereas the p(r) gain adjustment requires a distinct
trans-synaptic pathway involving β-catenin.