Dissecting midbrain and preoptic circuits that regulate social and nonsocial emotional states

解剖调节社交和非社交情绪状态的中脑和视前回路

• 批准号: 9765405
• 负责人: Jenna Ann McHenry
• 金额: $ 24.82万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9765405
• 关键词: Acute; Affective; Amygdaloid structure; Anatomy; Anhedonia; Animals; Anxiety Disorders; Appetitive Behavior; Area; Aversive Stimulus; Behavior; Behavioral; Biological Assay; Calcium; Cell Nucleus; Chronic; Complex; Corpus striatum structure; Cues; Data; Development; Disease; Dopamine; Economic Burden; Emotional; Exhibits; Food; Goals; Heterogeneity; Hypothalamic structure; Image; Impairment; Individual; K-Series Research Career Programs; Link; Major Depressive Disorder; Mammals; Medial; Mental disorders; Mentorship; Microscope; Midbrain structure; Modality; Molecular; Monitor; Motivation; Mus; Nature; Negative Valence; Neurons; Odors; Olfactory Cortex; Pathway interactions; Peptides; Personal Satisfaction; Phase; Positioning Attribute; Positive Valence; Prefrontal Cortex; Preoptic Areas; Process; Research; Research Personnel; Rewards; Schizophrenia; Sensory; Site; Social Behavior; Social Environment; Social Interaction; Stimulus; Sucrose; System; Training; Ventral Tegmental Area; approach behavior; autism spectrum disorder; dopaminergic neuron; emotional behavior; imaging approach; in vivo; insight; mesolimbic system; motivated behavior; neural circuit; neuropsychiatric disorder; optogenetics; programs; relating to nervous system; response; reward processing; social; social deficits

Dysregulated social and emotional processing is a debilitating issue across a wide range of neuropsychiatric disorders, including anxiety disorders, major depression, schizophrenia, and autism spectrum disorders. These disorders not only have severe impacts on individual well being but also represent a tremendous economic burden on the U.S. Since social and emotional disruptions often co-occur, a key question is how social processing neurons are intertwined with or embedded in positive and negative valence systems. This interplay is likely important to link social contexts with emotional representations and promote motivation. However, the precise functional neural circuitry that orchestrates these complex interactions remains unresolved and it is unclear whether social and nonsocial emotional information is processed through overlapping or distinct pathways. Recent technological developments have made it possible to combine calcium imaging and miniature epifluorescence microscopes to visualize the natural activity dynamics of individual neurons with anatomical and molecular precision, on a large scale in freely behaving animals. The goal of this proposed K99/R00 research is to use these approaches, in conjunction with in vivo optogenetic strategies, to chronically monitor and acutely manipulate the activity of precise neural circuits during social and nonsocial behaviors in mice. In particular, this project will focus on circuitry that connects the medial preoptic area (mPOA), an essential site for social behavior across mammals, with midbrain dopaminergic neurons that regulate motivational states. Activity-dependent monosynaptic tracing and combined optogenetic imaging approaches will also elucidate how salient sensory cues are transmitted to mPOA-midbrain circuits to adjust social and emotional states. Completion of the proposed aims is expected to be impactful because these studies will illuminate the causal and natural neural dynamics that underlie social and nonsocial emotional behavior. While the mesolimbic dopamine system has been well implicated in adaptive and maladaptive reward processing, it is unknown whether social motivation deficits are due to perturbations in specialized social pathways or due to more generalized reward disruptions. Identifying how these processes interact at the individual neuron level is of critical importance because without this information, we are unlikely to discover the ways in which certain social and nonsocial behavioral abnormalities arise. This career development award will provide the candidate with the technical training, conceptual background, and mentorship from renowned experts within the field. Ultimately, this training will uniquely position this young investigator to transition to an independent research program focused on investigating social and nonsocial emotional deficits that are common to many mental health disorders.

社交和情感处理失调是一个广泛的神经精神疾病问题 在一些实施方案中，所述药物组合物可用于治疗包括焦虑症、重性抑郁症、精神分裂症和自闭症谱系障碍在内的精神障碍。 这些疾病不仅对个人的健康有严重的影响，而且也代表了巨大的健康风险。 由于社会和情感的破坏往往同时发生，一个关键问题是如何 社会处理神经元与正价和负价系统交织在一起或嵌入其中。这 相互作用对于将社会环境与情感表征联系起来并促进动机可能很重要。 然而，协调这些复杂相互作用的精确功能神经回路仍然存在， 目前尚不清楚社会和非社会情感信息是否通过 重叠或不同的路径。最近的技术发展使联合收割机 钙成像和微型落射荧光显微镜，以可视化的自然活动动态， 个体神经元的解剖和分子精度，在大规模的自由行为的动物。的 这项K99/R 00研究的目标是使用这些方法，结合体内光遗传学， 策略，长期监测和急性操纵精确的神经回路的活动，在社会和 老鼠的非社会行为特别是，这个项目将集中在电路连接内侧视前区 区域（mPOA），哺乳动物社会行为的重要部位，中脑多巴胺能神经元， 调节动机状态。活动依赖性单突触追踪和组合光遗传学成像 方法也将阐明如何突出的感觉线索被传输到mPOA-中脑电路，以调整 社会和情感状态。预计完成拟议目标将产生影响，因为这些目标 研究将阐明社会和非社会情感的因果和自然神经动力学 行为虽然中脑边缘多巴胺系统已经很好地参与了适应性和适应不良 奖励处理，目前尚不清楚是否社会动机赤字是由于扰动的专门 社会途径或由于更普遍的奖励中断。确定这些过程如何相互作用， 单个神经元水平至关重要，因为没有这些信息，我们就不可能发现 某些社会和非社会行为异常的产生方式。这个职业发展奖 将为候选人提供技术培训，概念背景，并从著名的导师 该领域的专家。最终，这次培训将使这位年轻的调查员成为一名 一个独立的研究项目，专注于调查社会和非社会情感缺陷， 常见于许多精神疾病