Menglong Zeng received his doctoral training in Mingjie Zhang’s lab at the Hong Kong University of Science and Technology, where he applied biochemistry and structural biology to investigate how synaptic proteins interact to regulate synapse function. Specifically, he discovered that protein complexes in the postsynaptic density undergo a biophysical process named liquid-liquid phase separation, which allows synaptic proteins to self-assemble into membrane-less protein condensates to exert their synaptic functions with spatiotemporal precision, as a novel molecular mechanism underlying synapse formation and plasticity.
After completing his Ph.D., Zeng joined Guoping Feng’s lab at the Massachusetts Institute of Technology (MIT) for postdoctoral training in neuroscience, focusing on the synaptic mechanism of autism in vivo. He applied novel molecular techniques to investigate the architecture and function of excitatory synapses onto GABAergic interneurons, both in the healthy brain and in preclinical autism models. He was a fellow at the Simons Center for the Social Brain at MIT and also a fellow at the Tan-Yang Center for Autism Research at MIT.
Project: Characterizing the molecular architecture of excitatory synapses onto GABAergic interneurons
Normal brain function requires a delicate balance between excitatory and inhibitory neurons. While representing only a small portion of all neurons, GABAergic interneurons are essential to maintaining neural network excitation/inhibition balance and higher-order brain function. Unsurprisingly, GABAergic interneuron dysfunction is implicated in the pathophysiology of autism. A major category of autism risk genes encodes synaptic function regulators. However, the molecular architecture of 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.
How can we investigate the structure and function of minority cell-type specific synapses within an intact neural circuit? The current proposal will use a combination of in vivo proximity labeling, gene editing, expansion microscopy, electrophysiology and behavior to characterize the molecular architecture and function of excitatory synapses onto GABAergic interneurons, and to address the hypothesis that aberrant excitatory synaptic input onto GABAergic interneurons contributes to neural circuit dysfunction in autism.