New Horizons in Adult Neurogenesis

描述（由申请人提供）：这是NIDA独立科学家奖（K02）的续期申请。候选人Amelia J. Eisch博士是德克萨斯大学西南医学中心精神病学系的终身副教授。Eisch博士是了解海马可塑性某些形式（如成人海马神经发生和成瘾相关行为）之间相互关系的先驱。这个K02的第一个奖励期为Eisch博士提供了她需要的保护时间来完成她过去的目标，包括更新她在阿片类药物和神经发生方面的NIDA R01资助，获得额外的联邦资助，将她的工作从相关研究推进到更机械和“因果”研究，并被提升为副教授并获得终身职位。K02的更新是为了继续这段受保护的时间，并允许Eisch博士利用她在理解成人大脑中新神经元与成瘾之间拟议的相互作用方面所建立的势头。获得K02续期奖将使她继续免受行政负担的保护，从而使Eisch博士能够推进：(1)研究成人产生的神经元与成瘾相关行为之间的关系；(2)解剖成体海马神经元的细胞、分子和遗传控制；(3)在新神经元的翻译分析、超微结构分析和回路水平影响方面的新合作；(4)新技术在这些合作中的应用（BAC-TRAP、光遗传学、EM、电生理学）；(5)资助申请的数据收集：她现有的关于阿片类药物和神经发生的R01的10年更新，与海马神经发生的分子控制相关的新NIDA R01，以及与成人生成神经元的行为和回路水平影响相关的新NIDA R01。通过提供这段受保护的时间，艾施博士可以与她的合作者密切合作，并迅速推进她的新想法，从而使成瘾研究、干细胞生物学和神经科学领域成为一个整体。K02奖提供的稳定性和保护时间最终将支持至少两个探索成人生成的海马神经元与成瘾相关行为之间有趣关系的新项目。由于这些研究具有很大的潜力，可以提高我们对药物滥用影响大脑功能的复杂机制的理解，因此它们可能为药物成瘾和复发的治疗开辟新的途径。由于这些研究也将揭示成人生成的神经元如何影响复杂的行为——如药物/环境关联、药物寻求的消退和对压力的行为反应——它们将对未来利用神经干细胞修复受伤甚至成瘾的大脑以及我们对新神经元在成人大脑中可以/将做什么的理解非常重要。

DESCRIPTION (provided by applicant): This is a renewal application for a NIDA Independent Scientist Award (K02). The candidate, Amelia J. Eisch, Ph.D., is a tenured Associate Professor in the Department of Psychiatry at UT Southwestern Medical Center. Dr. Eisch is a pioneer in understanding the reciprocal relationship between certain forms of hippocampal plasticity such as adult hippocampal neurogenesis and behaviors relevant to addiction. The first award period of this K02 provided Dr. Eisch with the protected time she needed to accomplish her past goals, which included renewing her NIDA R01 grant on opiates and neurogenesis, securing additional federal funding, advancing her work from correlative to more mechanistic and "causative" studies, and being promoted to Associate Professor and receiving tenure. This K02 renewal is requested in order to continue this protected time and to allow Dr. Eisch to utilize the momentum she has established in understanding the proposed reciprocal role between new neurons in the adult brain and addiction. The receipt of a K02 renewal award would allow her continued protection from administrative burdens, and thus allow Dr. Eisch to advance: (1) research on the relationship between adult-generated neurons and behaviors relevant to addiction; (2) dissection of the cellular, molecular, and genetic control of adult-generated hippocampal neurons; (3) newly developed collaborations on translational profiling, ultrastructural analysis, and circuit-level impact of new neurons; (4) application of new techniques for these collaborations (BAC-TRAP, optogenetics, EM, electrophysiology); (5) data collection for grant applications: the 10-year renewal of her existing R01 on opiates and neurogenesis, a new NIDA R01 relevant to the molecular control of hippocampal neurogenesis, and a new NIDA R01 relevant to behavioral and circuit-level impact of adult-generated neurons. By providing this protected time, Dr. Eisch can work closely with her collaborators and rapidly advance her new ideas, thus benefitting the fields of addiction research and stem cell biology and neuroscience as a whole. The stability and protected time offered by this K02 award would ultimately support at least two new projects exploring the intriguing relationship between adult-generated hippocampal neurons and behaviors relevant to addiction. As these studies hold great potential to improve our understanding of the complex mechanisms by which drugs of abuse affect brain function, they therefore may open new avenues for treatment of addiction and relapse to drug seeking. As these studies also will also shed much-needed light on how adult-generated neurons influence complex behavior - such as drug/context association, extinction from drug-seeking, and behavioral response to stress - they will be important to future efforts to harness neural stem cells for repair of the injured, even addicted, brain and to our understanding of what new neurons can/will do in the adult brain.