The importance of inhibition
Yingxi Lin uses molecular, genetic, and electrophysiological methods to understand how inhibitory circuits form within the brain, and how they are shaped by activity and experience. Impaired inhibition has been implicated in many brain disorders, including epilepsy, anxiety disorders, schizophrenia and autism. The long term goal of Lin's research is to understand the pathways by which electrical activity shapes the development and maintenance of inhibitory circuits. Having a better understanding of the brain's inhibitory circuits may shed light on the origins and possible treatments of these diseases.
The brain's balancing act
Like a conventional electrical circuit, the brain uses both positive and negative components to amplify desirable signals while maintaining the overall stability of the system. Yingxi Lin wants to understand how this balance between excitation and inhibition is established during development and then maintained throughout life. The underlying molecular mechanisms are not well understood, but inhibitory neurons and their synaptic connections, which are readily modified by activity, are likely to play a critical role.
As a postdoctoral researcher, Lin identified a transcription factor known as Npas4 that appears to be a master regulator of inhibitory synapse development. In her laboratory at the McGovern Institute, she will use a combination of molecular, genetic, and electrophysiological approaches to understand how Npas4 controls this process, and to identify additional molecules that are important for inhibitory synapses. She also plans to study the development of inhibitory neurons, in particular how the function of these neurons is shaped by activity and experience during early life.
Disrupting the balance
Lin has shown that mice that are genetically engineered to lack Npas4 are prone to seizures, presumably because the balance between excitation and inhibition within the brain has been disrupted. These mice may be a useful model for human epilepsy, a possibility that Lin plans to explore in her future work. 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 has recently been shown 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.
Image: Kent Dayton