JUN 10, 2021 10:00 AM PDT
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GABA-receptive microglia selectively sculpt developing inhibitory circuits

Sponsored by: Vizgen
C.E. Credits: P.A.C.E. CE Florida CE
  • Klarman Cell Observatory, Broad Institute of Harvard and MIT
      After completing an engineering degree at Ecole Polytechnique, Paris, in 2012, Loic completed a master’s degree working on tissue engineering at Ecole Polytechnique of Montreal, then a phD In biomedical engineering at University of Montreal in 2019. His graduate work focused on developing optical approaches to target live cells chosen on visible criteria to both tag them without knowledge of their surface biochemistry and isolate them. Loic joined the broad institute in November 2019 and his work primarily focuses on applying optical approaches such as MERFISH to large-scale genomic screens.
    • Harvard Medical School and Broad Institute of Harvard and MIT
        Emilia started her studies in 2007 at the Sapienza University of Rome and was awarded a B.Sc. in Biological Sciences and a M.Sc. in Neurobiology. In 2011, she received a predoctoral fellowship from the Spanish National Research Council and joined the group of Beatriz Rico at the Institute of Neuroscience in Alicante (Spain). She moved with that group to the Centre for Developmental Neurobiology at King’s College London in 2014 where she terminated her doctoral training. Her graduate research work focused on the cellular and molecular mechanisms of inhibitory circuit development and plasticity in the cerebral cortex. She then received an EMBO postdoctoral fellowship to work on the cellular and molecular mechanism of microglia-inhibitory synapse interactions during development. Since 2017, she is a postdoctoral associate in Gord Fishell’s laboratory at Harvard Medical School and the Broad Institute. Over the years, she was awarded numerous prizes such as the Beddington Medal from the British Society for Developmental Biology and the Krieg Cortical Kudos Scholar Award from the Cajal Club.

      Date:  June 10, 2021
      Time: 10:00am (PDT),  1:00pm (EDT)
      Microglia, the primary brain macrophages, regulate a plethora of processes that impact the organization of neural circuits, including synapse pruning. Whether microglia are generic effectors of synapse pruning or if specialized microglia are able to discriminate between distinct synapse types is unknown. We found that GABA-receptive microglia selectively interact with inhibitory cortical synapses during a critical window of mouse postnatal development. Single cell RNA-seq and MERFISH profiling showed that ablation of microglial GABAB receptors cell-autonomously alters a transcriptional synapse remodeling program. As a result, loss of GABABRs within microglia alters inhibitory connectivity without impacting excitatory synapses and leads to behavioral abnormalities. These findings demonstrate that distinct microglia differentially engage with specific synapse types during development.
      Learning Objectives
      • Explain how MERFISH profiling can complement scRNA-seq data
      • Demonstrate how the selective communication between matching cell types regulates brain wiring
      • Reveal how early developmental events influence adult behavior
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