Synaptic contributions to sexually dimorphic circuit architecture

突触对性二态性电路结构的贡献

• 批准号: 10320388
• 负责人: Joseph Fossland Bergan
• 金额: $ 38.98万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10320388
• 关键词: Affect; Age; Aggressive behavior; Amygdaloid structure; Anatomy; Animals; Anorexia; Architecture; Aromatase; Axon; Behavior; Behavioral; Biology; Brain; Cells; Cognitive; Complex; Coupled; Cues; Data; Development; Endocrine; Environment; Estrogen Receptor alpha; Eye; Familiarity; Female; Gene Expression Profile; Goals; Gonadal Steroid Hormones; Health; Hormone Responsive; Human; Incidence; Individual; Investigation; Link; Location; Maps; Mediating; Medical; Mental Depression; Mental disorders; Morphology; Mus; Neuroanatomy; Neurons; Neurophysiology - biologic function; Neurosecretory Systems; Neurotransmitters; Output; Pattern; Persons; Phenotype; Physiology; Population; Process; Recording of previous events; Reproducibility; Research; Rest; Schizophrenia; Sensory; Severities; Sex Differences; Shapes; Social Behavior; Social Change; Social Network; Social support; Steroids; Stimulus; Synapses; Target Populations; Variant; Vertebrates; Viral; Work; autism spectrum disorder; behavioral response; experience; experimental study; genetic manipulation; insight; male; neural circuit; neurochemistry; rabies viral tracing; relating to nervous system; reproductive; response; sensory input; sensory integration; sex; sexual dimorphism; social; social organization; steroid hormone; tool

Project Summary/Abstract: The central goal of this work is to identify the configurations of neural circuit anatomy and function that support social behavior in males and females. Social behavior requires efficient integration of sensory cues from the external environment with an animal's internal physiology and neuroendocrine state. These computations often vary such that a single social stimulus can elicit markedly different behaviors in male and female animals. Here, we seek to establish how unique patterns of circuit connectivity shape sexually dimorphic circuit function. We will focus on aromatase–expressing neurons and estrogen receptor alpha–expressing neurons in the extended amygdala. The mouse is an ideal species for revealing the contribution of genetically defined populations of neurons to social behavior. In people, sex differences in behavior likely arise from complex interactions of biology and past experiences, but our social behavior networks share a deep evolutionary history with other vertebrates. In mice, reproducible sex differences in the size of specific populations of neurons, patterns of gene expression, targets of axonal projections, and dendritic architecture are well-established. When paired with powerful tools for genetic manipulation, these populations of neurons provide a unique opportunity for a systematic investigation of the relationships between neuroanatomical variation (at the level of circuits) and sex differences in behavior. Because the specific circuit configurations for either target population are not yet known in males or females, Aim I will use rabies tracing to map these circuits with an eye toward quantifying sexually dimorphic wiring patterns. Aim II investigates the neurochemical phenotype of neurons that provide input to aromatase- expressing and estrogen receptor alpha–expressing neurons in the extended amygdala. Quantifying the neurotransmitters used in these circuits will help us understand how activity at one node influences activity in its synaptically coupled partners. Aim III explores the moment-to-moment activity of these neural populations to reveal their respective contributions to processing social stimuli and producing social behavior. Together, these studies will advance our mechanistic understanding of how social information is transformed into sexually dimorphic cognitive, endocrine, and behavioral outputs.

项目摘要/摘要： 这项工作的核心目的是确定神经回路解剖和功能的配置 支持男性和女性的社会行为。社会行为需要有效地整合感官提示 具有动物内部生理和神经内分泌状态的外部环境。这些计算 通常会有所不同，以至于单一的社会刺激可以引起男性和女性动物的明显不同行为。 在这里，我们试图确定电路连通性的独特模式如何形态性二态电路函数。 我们将重点放在表达芳香酶的神经元和雌激素受体α的表达神经元 扩展的杏仁核。 小鼠是揭示神经元基因定义群体的贡献的理想物种 社会行为。在人们中，行为上的性别差异可能是由于生物学的复杂相互作用而引起的 过去的经验，但是我们的社会行为网络与其他脊椎动物共享了深厚的进化史。在 小鼠，神经元特定种群大小的可重复性差异，基因表达的模式， 轴突预测和树突状建筑的目标是良好的。与强大的工具配对时 对于遗传操作，这些神经元的种群为系统性提供了独特的机会 研究神经解剖变异（在电路级别）与性别差异之间的关系 行为。 因为在男性或 女性，目标我将使用狂犬病追踪来绘制这些电路，以量化性二态 接线模式。 AIM II研究了为芳香酶提供输入的神经元的神经化学表型 在扩展的杏仁核中表达和雌激素受体α的神经元。量化 这些电路中使用的神经递质将有助于我们了解一个节点的活动如何影响 它的突触耦合伙伴。 AIM III探讨了这些神经种群的瞬间活动 揭示他们对处理社会刺激和产生社会行为的贡献。一起， 这些研究将提高我们对社会信息如何转化为性别的机械理解 双态认知，内分泌和行为输出。