Brian Theyel, MD, PhD – Brown University
Abnormal ectopic action potentials in PV-INs: A novel pathophysiological mechanism in Dravet syndrome
Research Grant – $250,000, 2 years
Dravet syndrome, which is caused by a mutation in the SCN1A gene, is a debilitating illness that emerges during the first year of life. It causes seizures, setbacks during development, speech and language problems, and balance and walking issues. The scientific understanding of how the SCN1A gene changes brain activity is rapidly evolving. Each step brings us closer to discovering new medications for this illness, which often does not improve with current treatment options. Our work will explore whether a brain cell that is integrally important in Dravet syndrome symptomatology has disruptions that lead to specific malfunctions. In the course of this work we aim to determine how mutations in the SCN1A gene impact these cells’ normally powerful ability to “put the brakes on” the brain when it is too active. We believe that the loss of this “brake” may lead to seizures, and our experiments may yield important clues about how to get it working again.
About the Investigator:
Brian Theyel, MD, PhD is a Psychiatrist with a research interest in basic neuroscience. His work is targeted at understanding how unique properties of interneurons relate to neuropsychiatric diseases, with an emphasis on schizophrenia, autism spectrum disorder, and epilepsy. He has most recently discovered that an important inhibitory interneuron puts “the brakes” on brain activity by firing repeatedly in the “backward” direction when activity levels get too high. He is currently working to understand how these neurons sense elevated levels of brain activity and engage this mechanism, and believes that the myriad of mutations that both alter these inhibitory brain cells and are known to cause human disease might impact this property. His main methodologic research involves the whole-cell patch-clamp technique, local field potential recordings, in vitro neuroimaging, a cell-specific gene knockout strategy, and advanced neuroanatomical techniques. Dr. Theyel is also a clinician in the psychiatric emergency room at Butler Hospital, supervises residents in the Residency Continuity Clinic, teaches a several courses for psychiatry residents including a longitudinal seminar series entitled “Evidence-Based Medicine,” and co-directs the Brain & Behavior course at the Warren Alpert Medical School.