SCSB Lunch Series: Charactering the molecular architecture of excitatory synapse onto GABAergic interneurons

Date: Friday, May 19, 2023
Time: 12:00pm – 1:00pm
Location: SCSB Conference room 46-6011 + Zoom Meeting (https://mit.zoom.us/j/99475222915)

Speaker: Menglong Zeng, Ph.D.
Affiliation: Postdoctoral Fellow, Guoping Feng Laboratory, McGovern Institute, MIT

Talk title: Charactering the molecular architecture of excitatory synapse onto GABAergic interneurons

Abstract: Normal brain function requires a delicate balance between excitatory and inhibitory neurons. While only representing a small population of all neurons, GABAergic interneurons are essential to maintaining functional homeostasis across the brain. Genes encoding excitatory synaptic proteins tend to be one of the most prevalent hits in the screens of autism risk genes. However, the molecular architecture of excitatory synapses onto GABAergic interneurons has not been studied in sufficient details to establish the mechanistic insights needed to improve our understanding and treatment of autism.

In our study, we applied spatiotemporally precise proximity labeling techniques to uncover a novel assemblage of excitatory synaptic proteins onto parvalbumin interneurons. We discovered that parvalbumin interneurons have several strategies to distinguish their excitatory synapses molecularly and functionally from pyramidal neurons, possibly implicated in autism pathogenesis. We also combined gene editing, expansion microscopy and electrophysiology to study the structure and function of minority cell-type specific synapses within an intact circuit, to address the hypothesis that aberrant excitatory synaptic input onto interneurons contribute to neural circuit dysfunction in autism.