Multifaceted Functions of Mitochondria in Neuronal Synapses

Director's Seminar Series The Section on Synapse Development and Synaptic Plasticity led by Dr. Zheng Li is interested in the molecular and cellular mechanisms underlying synapse development and synaptic plasticity in normal brains and synaptopathology associated with psychiatric disorders. Our research shows that mitochondria, the vital organelles in eukaryotic cells, not only are essential for the general cell physiology, but also play multifaceted roles in synapses. In hippocampal neurons, the quantify of mitochondria in dendrites determines the density of synapses and dendritic spines. Mitochondria are permeabilized upon activation of NMDA receptors to release cytochrome c, which activates caspases to promote AMPA receptor endocytosis and long-term synaptic depression. Mitochondrial fission is induced when neurons are stimulated at gamma range (30-80 Hz) frequencies, which leads to translocation of mitochondria to synapses, and mitochondria fission is required for the maintenance of gamma oscillation, synchronized neural activities involved in cognitive processing and impaired in schizophrenia patients. Moreover, we found that dysbindin-1, a protein encoded by the schizophrenia risk gene DTNBP1 is required for mitochondrial fission during gamma oscillation, and that deficient dysbindin-1 in mice leads to inhibition of gamma oscillation. Dysbindin-1, therefore, may contribute to the cognitive impairment of schizophrenia patients by regulating mitochondrial fission and gamm...
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