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

描述（由申请人提供）：大量证据表明，扩展内侧杏仁核（MeA）介导行为的接近和回避方面。然而，特定的神经元群体以前没有被确定，选择性地响应社会刺激，是一个积极或消极的效价。对杏仁核价敏感神经元的识别和研究将为接近-回避行为和社交的规范性调节提供新的信息，并将对可能导致社交焦虑和社交行为临床相关缺陷的机制产生重要的见解。在这项资助的最初资助期间，我们建立了一个研究计划来研究社会性的神经机制，使用五种在物种典型群体大小方面差异很大的雀科物种（这些物种是领土，适度群居或高度殖民），但不是在其他重要方面（例如，所有物种都是一夫一妻制的）。这个系统为社会性的机制提供了许多见解，我们现在已经清楚地确定，效价敏感性（对正性刺激的选择性）是由终纹内侧床核（BSTm;扩展MeA的一个组成部分）中的催产素免疫反应（VT-ir）神经元表现出来的。这些神经元的响应曲线也不同的物种典型的组的大小，这样的同性同种刺激引起更强的反应，在群居物种比领土的物种。人类神经元几乎存在于所有陆地脊椎动物中，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BSTm神经元假设表现出对负价的敏感性。我们还将讨论一般的假设，1）多巴胺（DA）的输入影响VT神经元的社会引起的反应，和2）DA和VT相互作用，以调节接近回避。与VT一样，DA被认为会影响广泛的社会行为，并且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、给予激动剂和拮抗剂、广泛的行为评估和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敲低VT的产生，从而允许对特定VT细胞群进行功能研究。

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.