演讲人：Xiang Yu, Ph.D., Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, China

Molecular mechanism underlying experience-dependent neural circuit development and plasticity

Abstract:

When an infant is born, s/he already has the vast majority of neurons that will form her/his adult brain. Yet, most of these neurons have simple morphologies and are not well connected with each other. During the next several years of development, neurons extend their axonal and dendritic arbors and form extensive synaptic contacts with each other, in a process that is highly regulated by both intrinsic genetic programming and the external environment, as well as their interactions. My laboratory is interested in understanding the morphological and synaptic bases of experience-dependent neural circuit development, together with the molecular mechanisms mediating these processes. In previous work, we showed that the cadherin/catenin cell adhesion complex is a critical mediator of neural circuit development and plasticity, promoting spine stabilization during early development and competition-based spine maturation and/or pruning during adolescence/ adulthood. We also described a new form of global, experience-dependent crossmodal plasticity between the sensory cortices, and identified the neuropeptide oxytocin as a key mediator of this process. Putting our work in the context of existing knowledge, we proposed that early neural circuit wiring (first 3 weeks in mice, corresponding to first couple of years in humans) follows global plasticity rules (cm scale), as compared to local rules (μm scale) in the adult brain.

In recent work, we showed that systemic inflammation rapidly elevated (within 2 h) the level of cytokine CCL2 in mural cells of the microvessels in the brain. This CCL2 functioned as a neuromodulator to increase excitatory synaptic transmission in pyramidal neurons of multiple cortical and hippocampal regions. These results suggest that mural cell secreted CCL2 acts as an early sentinel during systemic injection and helps to coordinate immune responses of multiple cell types. A main effort in the lab is to identify more factors that regulate global neural circuit plasticity in different developmental/disease contexts and to determine their effects on neuronal, glial and vascular cells. We believe that a better understanding of the molecular mechanisms underlying early global neural circuit wiring and plasticity is critical to our basic understanding of brain function, and to potential treatment of developmental neurological disorders, including autism spectrum disorder, intellectual disability and schizophrenia.

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