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Molecular mechanism underlying activity-dependent neural circuit development - Xiang Yu
Stanford Neurosciences Institute Seminar Series Presents
Molecular mechanism underlying activity-dependent neural circuit development
Xiang Yu, Ph.D.
Senior Investigator, Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
Host: Jun Ding
Natural sensory experience is critical to neural circuit development and plasticity. To uncover the molecular mechanisms underlying activity-dependent neural circuit wiring, we established various neonatal sensory deprivation and enrichment models. Using these models, we identified an early form of global crossmodal plasticity in the mouse sensory cortices, whereby deprivation of sensory input in one sensory modality (eg somatosensation) reduced excitatory synaptic transmission not only in the correspondent sensory cortex (primary somatosensory cortex), but also crossmodally in other sensory cortices (primary auditory and visual cortices). We further demonstrated that this effect is mediated by the neuropeptide oxytocin, and that increased natural sensory experience through neonatal environmental enrichment can rescue the effects of sensory deprivation. Is crossmodal plasticity a general form of plasticity during early development? Are these other molecules that mediate this process? In work aimed at addressing this question, we showed that a single injection of LPS or Poly(I:C), treatments that mimic acute bacterial or viral infections, elevated the level of cytokine CCL2 in mural cells of the microvessels in the brain. This CCL2 rapidly (within 2 hours) induced elevation of excitatory synaptic transmission in pyramidal neurons of multiple cortical and hippocampal regions. We propose that this mural cell secreted CCL2 acts as an early sentinel during systemic injection and helps to coordinate immune responses of multiple cell types. Unlike the oxytocin-mediated crossmodal effects, with only occur during early development, CCL2-dependent global effects also occur in the adult brain. Together, our work demonstrates that there are global and crossmodal forms of plasticity in the brain, especially during early development. Defects in this mechanism likely contribute to developmental neurological disorders, including mental retardation, autism and schizophrenia. Our work also suggest increased natural sensory experience during early development as a potential treatment for these disorders.