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: 9974569
• 负责人: Jenna Ann McHenry
• 金额: $ 24.53万
• 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 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9974569
• 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令人衰弱的问题 疾病，包括焦虑症，严重抑郁症，精神分裂症和自闭症谱系障碍。 这些疾病不仅对个体健康产生了严重影响，而且代表了巨大的 由于社会和情感中断经常同时发生，美国对美国的经济负担，一个关键问题是如何 社会加工神经元与正价和负价系统中的交织或嵌入。这 相互作用对于将社会环境与情感表示并促进动机联系起来可能很重要。 但是，精确的功能性神经回路仍保持这些复杂相互作用 尚未解决，尚不清楚社交和非社会情感信息是否通过 重叠或不同的途径。最近的技术发展使得结合起来 钙成像和微型荧光显微镜，可视化自然活动动力学 具有解剖学和分子精度的单个神经元，在自由行为的动物中大规模地。这 该提出的K99/R00研究的目标是与体内光遗传学一起使用这些方法 在社交和 小鼠非社交行为。特别是，该项目将重点关注连接中间前的电路 区域（MPOA）是跨哺乳动物的社会行为的重要场所，中脑多巴胺能神经元 规范动机国家。依赖活性的单突触跟踪和混合光遗传成像 方法还将阐明如何将显着的感觉提示传输到MPOA-米德兰电路以调整 社会和情感状态。预计拟议目标的完成将是有影响力的 研究将阐明社会和非社会情绪的基础的因果和自然的神经动态 行为。虽然中唇多巴胺系统已充分涉及适应性和适应不良 奖励处理，尚不清楚社会动机赤字是否是由于专业人士的扰动 社会道路或由于更普遍的奖励中断。确定这些过程如何相互作用 单个神经元级别至关重要，因为没有这些信息，我们就不太可能发现 某些社会和非社会行为异常的方式出现了。这个职业发展奖 将为候选人提供著名的技术培训，概念背景和指导 该领域的专家。最终，这项培训将独特地定位这位年轻调查员，以过渡到 独立研究计划的重点是调查社会和非社会情绪缺陷 许多心理健康障碍共同。