Regulation of GABAergic Transmission by Neurotrophin-1 (NRG1), a Depression Risk Gene, and Its Receptor ErbB4
Interneurons in the cortex synchronize excitatory neuronal activity, optimize their output, and maintain the excitatory-inhibitory balance, playing a critical role in brain function. Recent studies suggest these neurons may also encode behavior. However, the precise mechanisms regulating interneurons remain unclear. Our experiments focused on neurotrophin (neurotrophin-1, NRG1) and its receptor tyrosine kinase ErbB4, investigating how they modulate interneuron function. We discovered that NRG1, released by pyramidal neurons, activates ErbB4 on interneurons, enhancing GABAergic synaptic transmission. This process influences learning, memory, attention, and fear prevention. I will present our laboratory's latest findings, emphasizing the role of NRG1-ErbB4 signaling in layer 1 interneurons. This layer is widely distributed across the neocortex of all mammals. Although structurally lacking excitatory neuronal cell bodies, it converges apical dendrites from deep-layer neurons and axonal inputs from multiple subcortical regions. Experiments show that most layer 1 interneurons express ErbB4. We discovered that chronic restraint stress specifically enhances excitatory synaptic inputs to layer 1 interneurons. This mechanism involves stress-activated neurons in the horizontal limb of the amygdala, which increase glutamate activity and release NRG1 onto ErbB4-positive layer 1 interneurons. These findings reveal a stress-sensitive “HDB-mPFC layer 1 interneuron” neural pathway. Given that NRGI and ErbB4 are risk genes for major depressive disorder, this study provides new insights into understanding its pathophysiological mechanisms.
Meilin, Distinguished Researcher and Founding Director of the Capital Medical Science Innovation Center, Chair Professor at Capital Medical University. Previously served as Assistant Professor and Associate Professor at the University of Virginia School of Medicine and the University of Alabama at Birmingham School of Medicine; Professor at the Medical College of Georgia, Director of the Institute of Molecular Medicine and Genetics, and Founding Director of the Department of Neuroscience and Regenerative Medicine; Holmes Chair and Department Chair in the Department of Neuroscience at Case Western Reserve University School of Medicine, and Founding Director of the Cleveland Brain Health Initiative. Returned to China full-time in March 2023.
Professor Mei Lin holds the following honors: Fellow of the American Association for the Advancement of Science (AAAS), Fellow of the American College of Neuropsychopharmacology (ACNP), NARSAD (National Alliance for Research on Schizophrenia and Depression) Distinguished Investigator, and Georgia Research Alliance Distinguished Scholar in Neuroscience.
Event Time: Wednesday, December 3, 10:00 AM - 11:30 AM
Event Format: Participants will gather in person to watch a live stream. The viewing location will be announced in the event notification group.
This event is limited to 50 participants on a first-come, first-served basis.
Event Registration
