of Work The purpose of this administrative supplement application is to provide support for Dr. Alexandra Bey, a psychiatry resident and neuroscience researcher, to expand her opportunities to carry out translational neuroscience research during her clinical training. By conducting the project outlined in this grant, Dr. Bey will gain invaluable experience in new scientific techniques, will study a behavior and its underlying neural dynamics extremely important to neuropsychiatric illnesses, and obtain personalized mentorship that will prepare her for an independent scientific career. To her accomplished skillset in molecular genetics and mouse behavior, she will develop electrophysiology and machine learning techniques in order to advance her ability to study neuronal circuits relevant to neurodevelopmental disorders. Through supervision by Dr. Kafui Dzirasa, Dr. Bey will receive intensive mentorship on experimental design, data analysis, manuscript publication, and grant-writing in order to prepare her to run a research group and compete for independent funding. Additionally, through regular counsel from a committee of preeminent clinician-scientists, Dr. Bey will obtain guidance and support for developing as a psychiatrist-neuroscientist as well as obtain relevant clinical exposure to patients with autism. Dr. Bey and Dr. Dzirasa have developed the following research project to investigate the neural dynamics of sleep. Furthermore, sleep as a behavior is quantifiable, translational, and frequently disrupted in many psychiatric and neurodevelopmental disorders. At present, there is very limited understanding of neural networks underlying sleep architecture. Dr. Bey?s experience with generating and characterizing different genetic mouse models of neuropsychiatric disorders uniquely poise her to advance her skillset to include techniques to truly dissect neural circuits, networks, and their dynamics. Utilizing Dr. Dzirasa?s expertise in in vivo electrophysiology, our collaborator Dr. David Carlson?s expertise in machine learning, we will support Dr. Bey in her efforts to: 1) obtain multisite in vivo electrophysiological recordings in mouse models of neuropsychiatric disease during sleep and wake states, 2) utilize machine-learning algorithms to identify altered neural circuit oscillations contributing to sleep architecture, and 3) extend this work to include a clinically relevant genetic manipulation to examine gene x stress interaction on the dynamics of sleep. Dr. Bey will be a key contributor to the development of each of these experiments and through their conduct, will develop expertise in measuring and understanding neural circuit function which will allow her to advance her career in studying the neurobiological basis of autism.
Many cortical and limbic brain regions including prefrontal cortex, amygdala, hippocampus, and thalamus work together to coordinate emotional, social and cognitive function in health and disease. In this study, we will discover the network-level mechanisms whereby fast interactions between these brain regions become altered in major depressive disorder. The discovery and validation of this ?depression brain-state? may facilitate the development of new therapeutics that ameliorate depression by directly modulating altered neural dynamics in the brain.
