title: Differential control of presynaptic efficacy by postsynaptic N-cadherin and β-catenin.
abstract: 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.
authors.affiliation: Medical Research Council Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London, London, UK.
authors.forename: Nathalia
authors.initials: N
authors.lastname: Vitureira
authors.forename: Mathieu
authors.initials: M
authors.lastname: Letellier
authors.forename: Ian J
authors.initials: IJ
authors.lastname: White
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Goda
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002478:Cells, Cultured; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D015820:Cadherins; D018091:Receptors, AMPA; D051176:beta Catenin