Functional neuroanatomy of circuits governing parental behavior

项目摘要/摘要 父母的照顾对于孩子的生存和幸福是必不可少的，尽管父母或其他成年人有时 对婴儿表现出忽视或攻击性行为。虽然母性行为已经被广泛研究， 对婴儿的激励性行为仍然知之甚少。我们的实验室最近证明了 结合分子、光遗传学和行为学技术了解内侧甘丙素神经元 视前区支配着父母行为的积极方面(Wu，Autry等人，2014年)。在当前应用程序中，我 计划对这种方法进行扩展，以揭示穹隆周围区域的一群神经元是如何 表达神经肽Urocortin-3(Ucn3)的下丘脑(PEFA)控制激动性婴儿定向行为。 我发现PEFA神经元在幼崽定向攻击时优先激活，而不是亲代 行为，激活的神经元主要与ucn3表达的神经元共定位。考虑到他们的参与 在焦虑和应激相关行为中的ucn3 PEFA神经元，结合我的结果，表明这些 在控制幼鼠定向激动性行为的神经元中，我假设PEFA ucn3神经元通常 在某些行为情境中，信号会被劫持，从而对狗狗行为产生负面影响 社交行为。我的K99/R00提案的目标是定义这一假定的解剖和功能 社会压力回路，并将这种解剖与婴儿在不同生理状态下的行为联系起来。 我的长期目标是成为神经科学领域的领先研究人员。我计划把重点放在 与社会行为相关的大脑中枢，以了解大脑如何处理和回应社会行为 以及在疾病状态下，这一过程是如何被破坏的。我相信这些研究将加强 我们对行为回路的理解，并为人类疾病的治疗创造了翻译途径。 为了实现这一目标，我需要在该领域最尖端的技术方面进行额外的培训。 我提出的行为电路分析的未来将依赖于改进的电路跟踪方法，在 活体记录技术，以及在行为背景下操纵神经元活动。我计划发展 在授奖的指导阶段，这些技术方面的专业知识。在博士的指导下。 Catherine Dulac，我将学习使用最复杂的病毒跟踪工具，通过与 罗立群博士和学习结合光遗传技术与四极管记录在共同指导下 内田直医生。我将寻求一位著名的压力专家约瑟夫·马兹朱布博士的指导，以及一个世界- 著名的精神病学疾病建模专家Rene Hen博士，将我的实验带到一个方向 翻译潜能研究产后抑郁症动物模型中回路的作用。有了这些 通过NIH K99/R00独立之路奖的支持获得的其他技能，我将 有资格执行这些目标，以便在理解社交过程如何成为 在人类精神障碍中被破坏。

Project summary/abstract Parental care is essential for the survival and well-being of young, though parents or other adults sometimes show neglect or aggressive behavior toward infants. While maternal behavior has been studied extensively, agonistic behavior toward infants remains poorly understood. Our lab has recently demonstrated the power of combining molecular, optogenetic, and behavioral techniques to understand how galanin neurons in the medial preoptic area govern positive aspects of parental behavior (Wu, Autry et al., 2014). In the current application, I plan to expand on this approach to uncover how a population of neurons in the perifornical area of hypothalamus (PeFA) expressing neuropeptide urocortin-3 (ucn3) governs agonistic infant-directed behavior. I found that PeFA neurons are preferentially active during pup-directed aggression, but not parental behavior, and the activated neurons largely colocalized with ucn3-expressing neurons. Given the involvement of ucn3 PeFA neurons in anxiety and stress-related behavior combined with my results implicating these neurons in governing pup-directed agonistic behavior, I hypothesize that PeFA ucn3 neurons that normally signal a “stressed” state are hijacked in some behavioral contexts to negatively impact pup-directed social behavior. The goal of my K99/R00 proposal is to define the anatomy and function of this putative social stress circuit and to connect this anatomy with infant-directed behavior in various physiological states. My long-term goal is to become a leading researcher in the field of neuroscience. I plan to focus on brain centers associated with social behaviors to understand how the brain processes and responds to social stimuli and how this processing becomes disrupted in disease states. I believe that these studies will enhance our understanding of behavioral circuits and create translational inroads for treatment of human disorders. To accomplish this goal, I will need additional training in the most cutting-edge techniques in the field. The future of behavioral circuit analysis such as I am proposing will rely on refined circuit tracing methods, in vivo recording techniques, and manipulating neuronal activity in behavioral contexts. I plan to develop expertise in these techniques during the mentored phase of the award. Under the primary mentorship of Dr. Catherine Dulac, I will learn to use the most sophisticated viral tracing tools available through collaboration with Dr. Liqun Luo and learn to combine optogenetic techniques with tetrode recordings under the co-mentorship of Dr. Nao Uchida. I will seek guidance from a leading expert in stress, Dr. Joseph Mazjoub, and a world- renowned expert in psychiatric disease modeling, Dr. Rene Hen, to take my experiments in a direction with translational potential examining the role of circuits in animal models of Postpartum Depression. With these additional skills gained through support by the NIH K99/R00 Pathway to Independence Award, I will be qualified to execute these goals to make great strides in understanding how social processing becomes disrupted in human psychiatric disorders.