From the elegant drawings of Ramon y Cajal, we learnt that neurons have beautiful and complex dendritic arbors, which are highly correlated with and specific to their locations and functions. As the main information receiving compartment of the neuron, dendrites and their elaborations are tightly intertwined with the formation of synapses, the basic information storage unit in the brain. Furthermore, both processes are highly regulated by neural activity, which itself gradually increase over the course of development, as neural circuits mature. Over the past decade, much insight has been gained into the molecular mechanisms through which neural activity regulates dendritic development, as well as how global alterations in neural activity result in compensatory changes in excitatory synaptic strengths. However, whether a potential link might exist between these activity-dependent morphological and electrophysiological changes remained unexplored.

In the January 15th issue of Neuron, work from the Laboratory of Dendritic Development and Neural Circuit Formation, mainly carried out by graduate students Yi-Rong Peng and Shan He under the supervision of Dr. Xiang Yu, in collaboration with the Professor Robert Malenka at Stanford University, identified coordinated and inversely correlated changes in dendritic morphology and unitary excitatory synaptic strength (mEPSC amplitude) following increased neural activity. They showed that over-expression of beta-catenin, a cell adhesion molecule that increases total dendritic length, mimics the effects of increased neural activity by scaling down mEPSC amplitudes, while postsynaptic expression of a protein that sequesters beta-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 arbor length and average mEPSC amplitude. Importantly, beta-catenin over-expression in vivo promoted dendritic growth and reduced mEPSC amplitudes. Interestingly, these neurons with larger dendritic arbors can still respond to subsequent activity blockade by scaling up their mEPSC amplitudes. These results suggest that during later stages of postnatal development, activity-dependent increases in dendritic arborization, mediated by the cadherin/catenin complex, are sufficient to activate mechanisms that limit total synaptic input and prevent over-excitation while leaving intact the ability to respond to further changes in neural activity. This phenomenon complements and adds to the armamentarium of mechanisms, such as Hebbian and homeostatic synaptic plasticity, which are believed to sculpt neural circuits during development.

This work was partly funded by grants from the Ministry of Science and Technology, the National Science Foundation of China, the Chinese Academy of Sciences and the Shanghai Municipal Government.