报告题目：Towards a genetic dissection of GABAergic circuitry in mouse cerebral cortex

报告人: 何苗博士

报告时间: 2012年10月23日（周二）下午14:00

报告地点: 苏州大学神经科学研究所会议室

报告人简介：

  Dr. Miao He is a postdoctoral fellow in Dr. Z. Josh Huang’s lab at Cold Spring Harbor Laboratory. She received her bachelor degree from department for Biological sciences and biotechnology in Tsinghua University and her doctoral degree from program of genetics in State University of New York at Stony Brook.

  Dr. He’s research in the last few years focused two interconnected projects aiming for a better understanding of the generation and maintenance of cortical GABAergic neuron diversity.

  The phenotypic properties of different cell types are largely acquired and maintained by unique combinations of expressed genes. To precisely and reliably identify and manipulate distinct interneuron subtypes, the Huang Lab utilized genetic targeting techniques which engage the intrinsic gene regulatory mechanisms that generate and maintain cell type identity and phenotypes to generate a resource of Credriver lines. These mouse models provided reliable experimental access and set the stage for a systematic and comprehensive analysis of cortical GABAergic circuits. Dr. He has made critical contribution towards establishment of the genetic targeting pipeline, and generated and characterized multiple knock‐in Cre lines.

  In parallel, Dr. He has developed a novel microRNA tagging and affinity‐purification (miRAP) strategy to systematically analyze miRNA expression in neuron subtypes within complex brain tissue. miRNAs are key regulators of gene expression, playing important roles in regulating neural development and plasticity, as well as progression of pathology in the neuronal system. A necessary step toward understanding of miRNAs function in the brain is to gain a comprehensive knowledge of their expression with cell type resolution in the relevant physiological conditions and developmental context. Dr. He’s strategy of molecular tagging and immune‐purification is based on the knowledge that mature miRNA is incorporated into the RNA‐induced silencing complex (RISC) where the miRNA and its mRNA target interact. Argonaute (AGO) proteins are at the core of RISC complex and directly bind miRNAs. She therefore tagged AGO2 with a GFP‐MYC fusion and targeted it expression to specific cell types through the Cre‐loxP binary system. Using miRAP, her studies of the neocortex and cerebellum reveal the expression of a large fraction of known miRNAs with distinct profiles in glutamatergic and GABAergic neurons and subtypes of GABAergic neurons.

  Dr. He’s future research program will aim at the genetic analysis of molecular mechanisms underlying neural circuit assembly and organization with an initial emphasis on miRNA, but will extend well beyond this niche. She will employ multidisciplinary experimental approaches centering on mouse genetic engineering and incorporate imaging, electrophysiology, genomics/epigenomics, and behavior analysis.A parallel effort will examine the aberrant function of cortical circuits from the angle of disturbances in distinct cell types in neurological disorders. 

神经科学研究所

2012-10-22