The importance of inhibition
Yingxi Lin uses molecular, genetic, electrophysiological and imaging methods to understand how brain circuits are shaped by experience during development and adulthood.
The main focus of the Lin lab is exploring the cellular and molecular mechanisms by which neuronal activity is coupled to modifications of neural circuits that lead to long term behavioural changes. One line of Lin’s research involves a neuronal transcription factor known as Npas4, which she originally identified as a regulator of inhibitory synapse formation. Npas4 is induced by electrical activity, and it appears to act as a master switch for controlling activity-dependent gene expression. The Lin lab has been studying Npas4’s roles in learning and memory in multiple brain regions using different behavioral paradigm. They have shown, for example, that Npas4 is induced in part of the hippocampus known as CA3 during the formation of contextual memories, and that mice lacking the Npas4 gene fail to form these memories. Lin’s work has revealed that Npas4 acts to control the activities of many other genes that respond to neural activity. She continues to study how these genetic pathways contribute to synaptic plasticity and to the encoding of new memories.
In another line of work, Lin is also developing new and highly sensitive genetic tools for marking active neurons, allowing researchers to identify and study the individual neurons that are involved in specific behavioral tasks. The Lin lab is actively investigating how experience-activated neurons participate in long term memory formation.
Disrupting the balance
Lin has found that mice lacking Npas4 are prone to seizures, presumably because the balance between excitation and inhibition within the brain has been disrupted. Impaired inhibition has also been implicated in many other brain disorders in humans, including anxiety disorders, schizophrenia, and autism. Indeed, one of the genes regulated by Npas4 is known to be a genetic risk factor for autism. As she learns more about the brain's inhibitory circuits, Lin hopes to shed new light on the origins and possible treatments of these diseases.
Yingxi Lin, who joined the McGovern Institute in 2008, is an associate professor in the Department of Brain and Cognitive Sciences at MIT. Originally from China, she received her bachelor's and master's degrees from Tsinghua University and her Ph.D. in biophysics from Harvard University. Prior to joining the McGovern Institute she was a postdoctoral fellow at Harvard Medical School and Children's Hospital Boston. She was named a John Merck Scholar in 2010.