Functional, Structural and Epigenetic Modifications of Cerebellar Purkinje Neurons in Alcohol-Dependent Mice

这个指导研究科学家发展奖（K01）应用程序支持职业发展

This Mentored Research Scientist Development Award (K01) application supports the career development and additional advanced technical training of Dr. Paula Zamudio-Bulcock to facilitate her transition to an independent academic investigator in the alcohol research field. She has extensive experience in ex-vivo slice electrophysiology, and during the mentoring period will gain experience with animal models of alcohol consumption and dependence. In addition, during the course of the proposed studies she will learn highly relevant techniques in the addiction research field including super-resolution confocal microscopy and epigenetic research methods. Importantly, Dr. Zamudio-Bulcock will also use the K01 protected training time to sharpen her career skills with a strong focus on manuscript preparation and submission, grantsmanship training and development of mentoring skills. Dr. Zamudio-Bulcock’s training will be supported by a strong institutional commitment to her career development and an outstanding and multifaceted mentoring team of leaders in the alcohol research field, each providing expert guidance throughout the progress of the proposed studies. The research plan evolved from Dr. Zamudio-Bulcock’s long standing interest in alcohol effects on the cerebellum and her experience studying the effects of acute and developmental alcohol exposures on cerebellar physiology. Thus, it is clearly distinguishable from the research focus of her mentor’s laboratory. Studies from the mentor and co-mentors have characterized functional, structural and epigenetic alterations after chronic alcohol exposure in brain regions implicated in alcohol consumption and dependence. Dr. Zamudio-Bulcock’s proposal will apply the methodologies used by her mentors to evaluate chronic alcohol–induced alterations in the cerebellum which, despite being highly sensitive to alcohol, has been understudied in the context of chronic alcohol use and dependence. The aims in this proposal have been tailored to test the hypothesis that chronic alcohol exposure leads to functional, structural and epigenetic alterations in the sole output of the cerebellar cortex, the GABAergic Purkinje cell. Importantly, the cerebellar cortex has been recently found to be a heterogeneous brain region with marked molecular, functional and structural differences among cerebellar lobules. Such differences are postulated to support the ample diversity of behavioral functions the cerebellum provides neuronal computation for. Given the functional connectivity of the posterior cerebellum with higher- order brain regions known to be affected in alcohol-dependent mice, the effects of chronic alcohol exposure will be studied in a sub-lobular specific manner with a focus on posterior lobules that are inter-connected with midbrain and cortical areas involved in reward and decision making. The opportunity to carry out these studies and engage in comprehensive career development training activities will provide a solid foundation for the candidate’s path to independence in the alcohol research field.