Neural circuit development requires concurrent morphological and functional changes. Here we identify coordinated and inversely correlated changes in dendritic morphology and mEPSC amplitude following increased neural activity. We show that over-expression of β-catenin, a molecule that increases total dendritic length, mimics the effects of increased neuronal activity by scaling down mEPSC amplitudes, while postsynaptic expression of a protein that sequesters β-catenin reverses the effects of activity on reducing mEPSC amplitudes. These results were confirmed immunocytochemically as changes in the size and density of surface synaptic AMPA receptor clusters. In individual neurons there was an inverse linear relationship between total dendritic length and average mEPSC amplitude. Importantly, β-catenin over-expression in vivo promoted dendritic growth and reduced mEPSC amplitudes. Together, these results demonstrate that coordinated changes in dendritic morphology and unitary excitatory synaptic strength may serve as an important intrinsic mechanism that helps prevent neurons from over-excitation during neural circuit development.

Formation of neural circuits depends on stable contacts between neuronal processes, mediated by interaction of cell adhesion molecules, including N-cadherin. In the present study, we found that activity-dependent dendrite arborization specifically requires Ncadherin-mediated extracellular neuron-neuron interaction, because the enhancement did not occur for neurons cultured in isolation or plated on an astrocyte monolayer and was abolished by a recombinant soluble N-cadherin ectodomain. Furthermore, depolarization elevated the level of membrane-associated cadherin/catenin complexes and surface N-cadherin. Importantly, surface N-cadherin elevation is specifically required for the maintenance of nascent dendrite arbors. Through loss-and gain-of-function approaches, we showed that N-cadherin-mediated dendrite growth requires association of the cadherin/catenin complex with the actin cytoskeleton. In summary, these results identify a previously unexplored and specific function for activity-induced, N-cadherin-mediated neuron-neuron contacts in the maintenance of dendrite arbors.cell adhesion molecule | catenin | actin D endrite growth and development are regulated by a combination of intrinsic programs and extrinsic signals, including neuronal activity, neurotrophins, morphogens, guidance cues, and cell adhesion molecules (CAMs), such as classical and seven-pass transmembrane cadherins (1-4). The establishment and maintenance of synaptic contacts between axons and dendrites also depend on CAMs, including neurexins/neurligins, EphB/ephrin-Bs, Neural-cadherin (N-cadherin), Ig superfamily members, and leucine-rich repeat containing synaptic adhesion molecules (5, 6). Importantly, the processes of axon/dendrite development and synapse formation are tightly correlated and regulated by neuronal activity (1,7). N-cadherin is a transmembrane CAM that interacts in a homophilic Ca 2+ -dependent manner through its extracellular ectodomains (8). Together with β-catenin and αN-catenin, it forms the cadherin/catenin complex, a main complex linking the extracellular environment to the actin cytoskeleton (9). The cadherin/catenin complex is present at high levels in both axons and dendrites (10), forming adherens junctions in epithelial cells and synaptic junctions in neurons.In the present study, we examined the function of N-cadherinmediated cell-cell interaction in the stabilization of dendritic arbors and in activity-dependent enhancement of dendritogenesis. Using a soluble N-cadherin ectodomain, we demonstrated a requirement for N-cadherin-mediated extracellular interaction in activity-dependent dendrite growth. Furthermore, by plating neurons in isolation, we showed that cell-cell contact is required for activity and N-cadherin-dependent dendrite growth. Finally, we showed that neuronal activity elevated surface N-cadherin level, an effect required for the maintenance of dendrite arbors. Together, these results identify a previously unexplored and specific function for activity-induced elevation of surface N-cadherin in the ma...