Functional Dissection of Neural Circuitry Underlying Parenting Behavior

项目摘要/摘要 在许多神经精神障碍中，社会功能障碍是一个突出的、令人衰弱的症状，例如 如自闭症谱系障碍、精神分裂症和严重抑郁障碍。目前，神经基础 人们对这些社会缺陷的认识很少，仍然缺乏有效的治疗方法。澄清 对社会行为的神经回路机制的研究将提高我们对疾病机制的理解 治疗神经精神障碍，促进开发有效的治疗方法。养育子女的行为是一种普遍的 以及进化上古老的社会行为，这些行为严重影响着后代的生存和福祉 动物种类繁多，从无脊椎动物到人类，都有显著的差异 不同性别和生殖状态之间的差异。尽管育儿行为被认为是由 在进化上保守的神经回路，这些回路的性质和功能在很大程度上仍然是未知的。 此外，不同性别父母教养行为差异显示的神经机制 人们对生理状态也知之甚少。解开这些问题将为我们提供对 父母养育行为的神经回路机制及其调控的基本原则 性两面性行为。这样的见解将提高我们对人类社会规律的理解 健康和疾病中的行为。最近，我们发现了GABA能的新的功能角色 小鼠杏仁内侧核(Mea)神经元在控制雌性和杀婴行为中的作用 男性的育儿行为。我们还全面鉴定了分子上的异质性GABA能 男性和女性的亚群都是如此。这些发现为深入研究 解剖大脑新发现的关键控制父母教养的区域的功能组织 杀婴行为。使用尖端功能操作和成像技术的组合，我们 目的建立不同GABA能亚群差异激活的新机制模型 在这项措施中，规范了相反的幼犬导向行为。我们将讨论一系列重要的问题， 该模型：(1)父母教养方式和杀婴方式是否受不同或相同手段的控制 亚群(目标1)？(2)MEA-GABA能神经元的下游神经回路是什么 育儿和杀婴行为(目标2)？(3)育儿和杀婴行为是如何由神经编码的？ Mea GABA能亚群的活动模式和传出投射(目标3)？要回答这些问题， 我们将对基因和投影定义的Mea GABA进行精确的功能操作 亚群及其轴突投射，并观察Mea-GABA能神经活动动力学 在自然幼犬定向行为期间自由行为动物的亚群及其投射。一起， 对这一模型的研究将对支配联系和激活性的神经回路产生关键的、新颖的见解。 对幼崽的行为和控制性二态社会行为的一般原则。

Project Summary/Abstract Impairments in social functioning is a prominent, debilitating symptom in many neuropsychiatric disorders, such as autism spectrum disorders, schizophrenia, and major depressive disorder. Currently the neural underpinnings of these social deficits are poorly understood, and effective therapeutic approaches are still lacking. Elucidation of the neural circuit mechanisms for social behaviors will improve our understanding of the disease mechanisms of neuropsychiatric disorders, facilitating the development of potent treatments. Parenting behavior is a prevalent and evolutionarily ancient social behavior that critically affects the survival and well-being of the offspring in a wide range of animal species from invertebrates to humans, and is characterized by remarkable differences between different sexes and reproductive states. Although parenting behavior is thought to be controlled by evolutionarily conserved neural circuits, the nature and functions of these circuits remain largely undefined. Furthermore, the neural mechanisms regulating the differential display of parenting behavior in different sexes and physiological states are poorly understood. Unraveling these questions will provide key insights into the neural circuit mechanisms underlying parenting behavior and the basic principles governing the regulation of sexually dimorphic behaviors. Such insights will improve our understanding on the regulation of human social behaviors in both health and disease. Recently, we have uncovered novel functional roles for GABAergic neurons in the mouse medial amygdala (MeA) in controlling parenting behavior in females and infanticidal and parenting behaviors in males. We have also comprehensively identified molecularly heterogeneous GABAergic subpopulations in both male and female MeA. These findings open up a unique opportunity for an in-depth dissection of the functional organization of a brain area newly identified to critically control parenting and infanticidal behaviors. Using a combination of cutting-edge functional manipulation and imaging techniques, we aim to develop a novel mechanistic model for how differential activations of distinct GABAergic subpopulations in the MeA regulate opposing pup-directed behaviors. We will address a series of important questions central to this model: (1) Are parenting and infanticidal behaviors controlled by different or the same MeA GABAergic subpopulations (Aim 1)? (2) What are the downstream neural circuits of MeA GABAergic neurons that mediate parenting and infanticidal behaviors (Aim 2)? (3) How are parenting and infanticidal behaviors encoded by neural activity patterns in MeA GABAergic subpopulations and efferent projections (Aim 3)? To answer these questions, we will perform precise, functional manipulations of genetically and projection-defined MeA GABAergic subpopulations and their axonal projections, and examine the neural activity dynamics of MeA GABAergic subpopulations and their projections in freely behaving animals during native pup-directed behaviors. Together, investigation of this model will yield key, novel insights into the neural circuitry governing affiliative and agonistic behaviors towards pups and the general principles underlying the control of sexually dimorphic social behaviors.