Functional neuroanatomy of circuits governing parental behavior

控制父母行为的回路的功能神经解剖学

基本信息

批准号：
10085730
负责人：
Anita Autry
金额：
$ 8.76万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-11 至 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10085730
关键词：
Acute Adrenal Glands Adult Affect Aggressive behavior Agonistic Behavior Anatomy Animal Behavior Animal Model Anxiety Area Award Behavior Behavioral Binding Brain Brain region CRF receptor type 2 Caring Cells Child Rearing Chronic stress Collaborations Corticotropin-Releasing Hormone Disease Disease model Dyes Family Female Future Galanin Goals Human Hypothalamic structure Immediate-Early Genes Infant Knock-out Laboratories Lactation Learning Major Depressive Disorder Maps Maternal Behavior Medial Mental disorders Mentors Mentorship Methods Molecular Mus Neuroanatomy Neurons Neuropeptides Neurosciences Outcome Output Parents Partner in relationship Paternal Behavior Pathway interactions Personal Satisfaction Phase Physiological Population Postpartum Depression Preoptic Areas Process Property Rabies Regulation Research Personnel Role Sensory Signal Transduction Social Behavior Specificity Stress Synapses Techniques Training United States National Institutes of Health Viral anxiety-related behavior awake behavioral response biological adaptation to stress experimental study in vivo male molecular subtypes neglect nerve supply neuromechanism optogenetics overexpression postsynaptic neurons presynaptic pup response restraint stress skills social social stress stimulus processing stress state therapeutic target tool urocortin

项目摘要

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.

项目概要/摘要父母的照顾对于年轻人的生存和福祉至关重要，尽管父母或其他成年人有时对婴儿表现出忽视或攻击行为虽然主要研究了母亲的行为，我们的实验室最近证明了对婴儿的攻击行为的力量仍然知之甚少。结合分子、光遗传学和行为技术来了解内侧甘丙肽神经元如何视前区控制父母行为的积极方面（Wu，Autry 等，2014）。计划扩展这种方法，以揭示穹窿周围区域的神经元群体如何表达神经肽 urocortin-3 (ucn3) 的下丘脑 (PeFA) 控制婴儿的激动性行为。我发现 PeFA 神经元在幼崽的攻击行为中优先活跃，但在父母的攻击行为中则不然行为，并且激活的神经元很大程度上与表达 ucn3 的神经元共定位。 ucn3 PeFA 神经元在焦虑和压力相关行为中的作用以及我的结果表明这些神经元在控制幼崽定向的竞争行为中，我驱动了通常情况下的 PeFA ucn3 神经元发出“压力”状态的信号在某些行为环境中被劫持，从而对小狗产生负面影响我的 K99/R00 提案的目标是定义这个假设的解剖结构和功能。社会压力回路，并将这种解剖结构与各种生理状态下的婴儿导向行为联系起来。我的长期目标是成为我计划专注的神经科学领域的领先研究员。与社会行为相关的大脑中枢，以了解大脑如何处理和响应社会行为我相信这些研究将加强刺激以及这种处理在疾病状态下如何被破坏。我们对行为回路的理解并为治疗人类疾病创造转化进展。为了实现这一目标，我需要接受该领域最前沿技术的额外培训。我所提议的行为回路分析的未来将依赖于精细的回路追踪方法，例如我计划开发体内记录技术以及在行为环境中操纵神经活动。在该奖项的指导阶段，在博士的主要指导下获得了这些技术的专业知识。凯瑟琳·杜拉克（Catherine Dulac），我将通过与罗立群博士并在罗立群博士的共同指导下学习将光遗传学技术与四极管记录相结合我将向压力领域的权威专家 Joseph Mazjoub 博士和世界级专家寻求指导。著名精神疾病模型专家 Rene Hen 博士为我的实验指明了方向转化潜力检查回路在产后抑郁症动物模型中的作用。通过 NIH K99/R00 独立之路奖的支持获得的额外技能，我将有资格执行这些目标，以在理解社会处理如何变得方面取得重大进展人类精神疾病受到干扰。