beta-Catenin regulates excitatory postsynaptic strength at hippocampal synapses.
The precise contribution of the cadherin-beta-catenin synapse adhesion complex in the functional and structural changes associated with the pre- and postsynaptic terminals remains unclear. Here we report a requirement for endogenous beta-catenin in regulating synaptic strength and dendritic spine morphology in cultured hippocampal pyramidal neurons. Ablating beta-catenin after the initiation of synaptogenesis in the postsynaptic neuron reduces the amplitude of spontaneous excitatory synaptic responses without a concurrent change in their frequency and synapse density. The normal glutamatergic synaptic response is maintained by postsynaptic beta-catenin in a cadherin-dependent manner and requires the C-terminal PDZ-binding motif of beta-catenin but not the link to the actin cytoskeleton. In addition, ablating beta-catenin in postsynaptic neurons accompanies a block of bidirectional quantal scaling of glutamatergic responses induced by chronic activity manipulation. In older cultures at a time when neurons have abundant dendritic spines, neurons ablated for beta-catenin show thin, elongated spines and reduced proportion of mushroom spines without a change in spine density. Collectively, these findings suggest that the cadherin-beta-catenin complex is an integral component of synaptic strength regulation and plays a basic role in coupling synapse function and spine morphology.
Medical Research Council Laboratory for Molecular Cell Biology and Cell Biology Unit, Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, United Kingdom.
Takashi
T
Okuda
Lily M Y
LM
Yu
Lorenzo A
LA
Cingolani
Rolf
R
Kemler
Yukiko
Y
Goda
D000818:Animals; D002478:Cells, Cultured; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D051381:Rats; D013569:Synapses / Q000502:physiology*; D051176:beta Catenin / Q000502:physiology*
D051176:beta Catenin