Valence Coding and Regulation of Approach-Avoidance in Social and Asocial Species

社会性和非社会性物种的接近回避的价编码和调节

• 批准号: 7099208
• 负责人: JAMES L GOODSON
• 金额: $ 29.63万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-12-15 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7099208
• 关键词: RNA interference; amygdala; animal communication behavior; behavior test; behavioral /social science research tag; dopamine; ethology; experimental brain lesion; fos protein; immunocytochemistry; in situ hybridization; neural information processing; neuroanatomy; neurochemistry; neuroregulation; nucleic acid probes; protein protein interaction; reinforcer; sex hormones; social behavior; social behavior disorders; social cooperation; songbirds; species difference; tyrosine 3 monooxygenase; vasopressins

DESCRIPTION (provided by applicant): Numerous lines of evidence suggest that the extended medial amygdala (MeA) mediates both approach and avoidance aspects of behavior. However, specific neuronal populations have not previously been identified that respond selectively to social stimuli that are of a positive or negative valence. The identification and investigation of valence-sensitive amygdalar neurons would provide novel information about normative regulation of approach-avoidance behavior and sociality, and would generate important insights into mechanisms that may underlie social anxiety and clinically-relevant deficits in social behavior. During the initial funding period for this grant, we established a research program to examine neural mechanisms of sociality, using five finch species that differ strongly in their species-typical group sizes (the species are territorial, modestly gregarious, or highly colonial), but not in other important ways (e.g., all of the species are monogamous). This system is providing numerous insights into the mechanisms of sociality, and we have now clearly established that valence sensitivity (selectiveness for positive stimuli) is exhibited by vasotocin- immunoreactive (VT-ir) neurons in the medial bed nucleus of the stria terminalis (BSTm; a component of the extended MeA). Response profiles of these neurons also differ in relation to species-typical group size, such that same-sex conspecific stimuli elicit stronger responses in gregarious species than in territorial species. Homologous neurons are found in virtually all land vertebrates, including humans. The experiments proposed here will further elucidate functional properties of valence-sensitive VT neurons, and will seek to identify and characterize BSTm neurons hypothesized to exhibit a sensitivity to negative valence. We will also address the general hypotheses that 1) dopamine (DA) inputs influence socially-elicited responses of VT neurons, and 2) DA and VT interact to regulate approach-avoidance. As with VT, DA is known to influence a wide range of social behaviors, and DA plays a major role in generating positive affective states. We will employ a diversity of approaches, including the use of DA lesions, administrations of agonists and antagonists, extensive behavioral assessments, and analyses of Fos induction (inclusive of multi-labeling with VT and TH). We additionally propose the development of VT RNA interference that will enable us to specifically knock down VT production, thus allowing the functional investigation of specific VT cell groups.

描述（由申请人提供）：许多证据表明，扩展的内侧杏仁核（MEA）介导了行为的方法和回避方面。但是，以前尚未确定特定的神经元种群对呈正价或负面价的社会刺激有选择性反应。对价敏感的杏仁核神经元的识别和研究将提供有关避免进近行为和社会性规范性调节的新信息，并将对可能是社交焦虑和社会行为中临床上不相关的机制产生重要的见解。在该赠款的最初资助期间，我们建立了一项研究计划来检查社会性的神经机制，使用五个芬奇物种在物种典型的群体规模上有很大差异（该物种是领土，谦虚或高度殖民的），但并非以其他重要的方式（例如，所有物种都是一夫一妻）。该系统为社会性机制提供了许多见解，我们现在已经清楚地表明，在Stria terminalis的内侧床核中，血管蛋白菌免疫反应性（VT-IR）神经元表现出价敏感性（阳性刺激的选择性）（vt-ir）神经元（BSTM; BSTM; BSTM; BSTM; A ebsended Mea的一部分）表现出​​来。这些神经元的反应谱在与物种典型的群体大小的关系方面也有所不同，因此相同的同性刺激会在群落物种中与领土物种相比，在人群中产生更强的反应。在包括人类在内的几乎所有陆地脊椎动物中都发现了同源神经元。此处提出的实验将进一步阐明对价敏感VT神经元的功能特性，并将寻求识别和表征所假设的BSTM神经元，以表现出对负价的敏感性。我们还将解决总体假设，即1）多巴胺（DA）输入会影响VT神经元的社会释放反应，以及2）DA和VT相互作用以调节避免接近的反应。与VT一样，DA也会影响广泛的社会行为，DA在产生积极的情感状态中起着重要作用。我们将采用多种方法，包括使用DA病变，激动剂和拮抗剂的管理，广泛的行为评估以及FOS诱导分析（包括使用VT和TH的多标记）。我们还提出了VT RNA干扰的发展，这将使我们能够专门击倒VT的产生，从而允许对特定VT细胞组的功能研究。