Translational Studies of Brain Circuitry Disrupted by Alcoholism

描述（由申请人提供）：本K05继续申请是为了响应NIAAA计划公告（PA-12-148）的高级科学家奖，并代表了我作为主要或指定研究者的nih资助项目的综合。作为斯坦福大学医学院精神病学和行为科学系的教授，我是一名科学家，负责酒精中毒和衰老对大脑结构和功能的影响的人类和动物研究。这个申请的主要目的是将我作为一个科学家的角色扩展到一个导师的角色，在我的神经科学项目的各个方面教授和领导发展中的神经科学家。我的研究项目使用定量行为神经科学方法，辅以结构和功能磁共振成像（MRI和fMRI）、扩散张量成像（DTI）和脉冲连续动脉自旋标记（PCASL），目的是表征酒精中毒本身以及与发育和衰老相关的大脑变化相互作用的受影响大脑区域。我的学员将接受我研究各方面的培训，重点是对具有影像学背景的学员进行行为实验培训，对具有心理学和行为学背景的学员进行影像学培训。我建议每5年有5名学员，每3 - 5年，所有学员都完成博士后培训，现在开始成为独立的研究者。斯坦福大学的神经科学研究社区是动态的、多方面的、互动的，吸引了各行各业最聪明的学生、研究员和教师。我在自己的院系以及放射学、神经科学项目和SRI国际都有重要的合作。我研究的基础是获得先进的神经成像设备和专业知识，用于我自己和我的学生的人类和动物研究。我的实验室的综合资源，跨站点的神经成像设备，以及大斯坦福社区特殊的正式和非正式神经科学教育项目，为我的学生提供了一个丰富的环境。酒精中毒的常见但不为人所知的不良后果是认知、感觉和运动功能的细微但显著的损害。确定哪些脑系统的支持功能保持相对完整，哪些脑系统在酒精中毒中因正常衰老加剧而受损，或受酒精相关的偏离正常发育轨迹的影响，是设计康复努力以招募完整的脑系统来补偿受损脑系统的关键一步。让下一代学员参与并进一步在这些领域开展自己的研究，对成瘾的公共卫生问题具有显著的潜在相关性。

DESCRIPTION (provided by applicant): This K05 continuing application is in response to an NIAAA Program Announcement (PA-12-148) for a Senior Scientist Award and represents a synthesis of NIH-funded projects on which I am principal or named investigator. As a professor in the Department of Psychiatry and Behavioral Sciences at Stanford University School of Medicine, I am a scientist who conducts translational human and animal studies of the effects of alcoholism and aging on brain structure and function. The primary objective of this application is to extend my role as a scientist to that of a mentor who teaches and leads developing neuroscientists in all aspects of my neuroscience program. My program of research uses quantitative behavioral neuroscience approaches that are complemented with structural and functional magnetic resonance imaging (MRI and fMRI), diffusion tensor imaging (DTI), and pulse continuous arterial spin labeling (PCASL) with the aim of characterizing affected brain regions in alcoholism itself and in interaction with brain changes associated with development and senescence. My mentees will receive training in all aspects of my research with emphasis on behavioral experimental training for mentees with imaging backgrounds and training in imaging for mentees with psychology and behavioral backgrounds. I propose to have five mentees in each of the 5 years of the award, each for three to five years, all having completed postdoctoral training and now embarking on becoming independent investigators. Stanford University's neuroscience research community is dynamic, multifaceted, and interactive and attracts the brightest students, fellows, and faculty at all levels of career development. I have major collaborations in my own department as well as in Radiology, the Neuroscience Program, and SRI International. Fundamental to my research is access to advanced neuroimaging facilities and expertise for my own and my mentees' human and animal studies. The combined resources of my laboratory, across-site neuroimaging facilities, and the exceptional formal and informal neuroscience educational programs of the greater Stanford community provide a rich environment for my mentees. Common but often unrecognized untoward consequences of alcoholism are subtle but functionally significant impairments in cognitive, sensory, and motor functions. Identification of the brain systems supporting functions that remain relatively intact and those that are damaged in alcoholism with exacerbation from normal aging or subject to alcohol-related deviations from normal developmental trajectories is a crucial step in designing rehabilitation efforts for recruiting intact brain systems to compensate for damaged ones. Having the next generation of mentees engage in and then further their own research in these areas has notable potential relevance to public health concerns of addiction.