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

Nat Neurosci. 2011 Dec 4;15(1):81-9. doi: 10.1038/nn.2995.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / metabolism*
  • Cells, Cultured
  • Hippocampus / metabolism
  • Mice
  • Neurons / metabolism*
  • Rats
  • Receptors, AMPA / metabolism
  • Synapses / metabolism*
  • Synaptic Transmission / physiology*
  • Synaptic Vesicles / metabolism
  • beta Catenin / metabolism*


  • Cadherins
  • Receptors, AMPA
  • beta Catenin