The regulation of synaptic transmission and neural circuit function

National Institute Of Neurological Disorders And Stroke

Investigators

Linked publications & trials

Abstract

The lab is interested in understanding molecular and cellular mechanisms underlying synapse formation and synaptic plasticity, and in the long term elucidating synaptic mechanisms underlying neuronal circuit function and dysfunction in animal behavior and brain illness. We believe that our studies will provide fundamental insights into neural underpinnings for brain cognition and will help identify synaptic and neural circuit malfunctions that are involved in many neurological and mental disorders, such as epilepsy, Alzheimer's disease, anxiety and depression, and autism. Specifically, during the 2025 fiscal year, we have made following progress: For research Aim 1, which focuses on identifying and characterizing novel proteins that bind to GABA-A receptors and regulate inhibitory transmission, we have identified a new transmembrane protein, TMEM132B, that binds to GABA-A receptors and regulates inhibitory transmission. Importantly, TMEM132B also enhances alcohol-induced potentiation of GABA-A receptor mediated currents. Currently, a manuscript summarizing this work has been published in Cell in November 2024. In addition we have made major progress in determining the regulation of GABA-A receptor psychopharmacology in vivo by Shisa7 that also interacts with GABA-A receptors. For research Aim 2, we investigated the mechanisms for the regulation of GABAergic synapse development and function in health and disease. Specifically, we have determined the role of NL2 C-terminus in inhibitory synapse development and social behavior, leading to a publication in Journal of Neuroscience in 2025. For research Aim 3, we have identified a population of neurons in the central nucleus of amygdala that is critical for the regulation of general anesthesia by Shisa7 and that is important for both hypnotic and analgesic effects of general anesthetic, diazepam. In the FY2025, we have also made exciting progress in collaboration projects in FY2025. We have collaborated with Dr. Katherine Roche group at NINDS, NIH to study Neuroligins, leading to one publication in eNeuro and another manuscript currently under review. In addition, we have collaborated with Dr. Yan Li from NINDS, NIH to characterize neuronal GABA-A receptors complexes.