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）：大量证据表明扩展的内侧杏仁核（MeA）介导行为的接近和回避方面。然而，之前尚未发现特定的神经元群能够选择性地响应正价或负价的社会刺激。对价敏感杏仁核神经元的识别和研究将提供有关回避行为和社交性的规范调节的新信息，并将产生对可能构成社交焦虑和临床相关社交行为缺陷的机制的重要见解。在这笔赠款的最初资助期间，我们建立了一个研究计划来检查社会性的神经机制，使用了五种雀类，这些雀类的物种典型群体规模差异很大（这些物种具有领地性、适度群居性或高度殖民性），但是不是以其他重要方式（例如，所有物种都是一夫一妻制）。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确定，终纹内侧床核（BSTm）中的加压素免疫反应性（VT-ir）神经元表现出价敏感性（对正刺激的选择性） ; 扩展 MeA 的一个组成部分）。这些神经元的反应特征也因物种典型群体大小而异，因此同性同种刺激在群居物种中比在领地物种中引起更强的反应。几乎在所有陆地脊椎动物中都发现了同源神经元，包括人类。这里提出的实验将进一步阐明价敏感 VT 神经元的功能特性，并将寻求识别和表征假设对负价表现出敏感性的 BSTm 神经元。我们还将讨论以下一般假设：1) 多巴胺 (DA) 输入影响 VT 神经元的社会诱发反应，2) DA 和 VT 相互作用以调节接近回避。与 VT 一样，DA 会影响广泛的社会行为，并且 DA 在产生积极情感状态方面发挥着重要作用。我们将采用多种方法，包括使用 DA 损伤、施用激动剂和拮抗剂、广泛的行为评估以及 Fos 诱导分析（包括 VT 和 TH 的多重标记）。我们还建议开发 VT RNA 干扰，这将使我们能够特异性地抑制 VT 的产生，从而可以对特定 VT 细胞群进行功能研究。