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In vitro and in vivo functional assessment of neuropsychiatric disease-related synaptic gene mutations

Principal Investigator:
  • Yicheng Xie, Brain Research Centre, University of British Columbia
  • Djavad Mowfaghian Centre for Brain Health

Project Overview

Dr. Xie’s research focuses on the functional assessment of neuropsychiatric disease related synaptic genes – MDGA1 and 2. MDGAs bind to critical neuron synaptic proteins – Neuroglin (NLGN), disrupting the binding between NLGN and Neurexin (NRXN), so suppressing synaptogenesis. Mutations (missense or truncation) of MDGA1 and 2 have been found in schizophrenic and autistic patients, respectively. Interestingly, MDGA1 preferentially binds to NLGN2, disrupt inhibitory synaptic formation, whereas MDGA2 binds to both NLGN1 and 2, so disrupt both inhibitory and excitatory synaptic formation. Therefore, he is studying the mechanisms of the selectivity of MDGA1 and 2, trying to decode the mechanisms of inhibition and excitation balance (E/I balance) in the brain. Moreover, using transgenic mice with conditional knockout of MDGA1 and 2, he will be able to functionally assess how MDGA1 and 2 deletion at different development stages could affect E/I balance in the brain with various in vivo electrophysiological and imaging tools. I hope my research could add to the basic neurological knowledges regarding how E/I balance is forming in the brain, and how the synaptic gene – MDGA regulates the excitability of the brain in mice.