Social and Motivational Properties of Vasoactive Intestinal Polypeptide Circuits

血管活性肠多肽回路的社会和动机特性

• 批准号: 8269653
• 负责人: JAMES L GOODSON
• 金额: $ 38.27万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8269653
• 关键词: Address; Aggressive behavior; Animals; Antisense Oligonucleotides; Anxiety; Area; Behavior; Behavioral; Binding Sites; Birds; Brain; Caring; Cell Count; Cells; Courtship; Data; Ear; Ecology; Environment; Exhibits; Exposure to; Family; Female; Fiber; Finches; Goals; Grouping; Hypothalamic structure; In Situ Hybridization; Label; Lateral; Mammals; Mental Depression; Mental Health; Mental disorders; Messenger RNA; Motivation; Neurons; Pair Bond; Pattern; Physiological; Play; Post-Traumatic Stress Disorders; Process; Production; Prolactin; Property; Proteins; Protocols documentation; Proxy; Regulation; Role; Sex Behavior; Site; Social Behavior; Social Environment; Stimulus; Stress; Structure; Testing; Variant; Vasoactive Intestinal Peptide; Vertebrates; Viola; Withdrawal; brain tissue; density; immunocytochemistry; male; motivational processes; neurobehavioral; neuromechanism; offspring; parental influence; psychologic; receptor; relating to nervous system; research study; response; sex; social; social integration; species difference; tool; zebra finch

DESCRIPTION (provided by applicant): Vasoactive intestinal polypeptide (VIP) is a major regulator of prolactin secretion in vertebrates, and is thus an essential contributor to the central regulation of parental care, even if only via its effects on prolactin. VIP receptors and fibers are found at high density in all brain area that are known to contribute to parental care, and throughout social behavior circuits more generally. In addition to hypothesized effects on parental behavior, there are excellent reasons to expect that VIP circuits also influence aggressive behavior, sociality, sexual behavior and pair bonding; and more general aspects of motivation and anxiety. The finch family Estrildidae is an ideal group for testing such diverse hypotheses, given that 1) zebra finches (Taeniopygia guttata) exhibit an extraordinary diversity of robust, quantifiable behaviors, and 2) several estrildid species are available that exhibit massive differences in species-typical group size, while still being closely matched to the zebra finch in most other aspects of behavior and ecology. Recent findings in finches demonstrate that choice of group size is titrated independently from simple affiliation, suggesting the presence of important but largely unexplored neural mechanisms of sociality. Social anxiety and withdrawal are commonly observed in conjunction with a variety of psychiatric disorders and psychological problems, and thus this proposal will explore neurobehavioral mechanisms that are likely fundamental to a healthy social behavior, and identify variations that may predispose people to social avoidance. Limbic-hypothalamic circuits in birds and mammals are strongly conserved, allowing the behavioral robustness of finches to inform relevant studies in mammals. Specific Aim 1 will employ central antagonism of VIP receptors and site-specific knockdown of VIP production using antisense oligonucleotides to examine effects on sociality, anxiety, nesting, and parental care in male and female zebra finches. Focal observations will also be conducted in a colony environment, allowing for the quantification of more than 20 behaviors, including pair bonding. Specific Aim 2 will employ similar manipulations for tests of aggression and anxiety-like behavior in the highly territorial violet-eared waxbill (Uraeginthus granatina). Specific Aim 3 will employ a combined protocol for in situ hybridization and immunocytochemistry to determine which VIP cell groups show increased Fos activation in response to 1) nest-building in male and female zebra finches, 2) courtship in male zebra finches, and 3) aggressive interactions and non-social defense in violet-eared waxbills. Finally, Specific Aim 4 will 1) examine the Fos activation of VIP cell groups following exposure to same-sex stimuli in three gregarious and two territorial species, and 2) quantitatively compare the distribution of VIP mRNA in the same animals. The density of VIP binding sites in the lateral septum is positively related to sociality in these species, suggesting that VIP may play an important role in differentiating the behavioral and/or physiological responses of gregarious and relatively asocial animals. Such processes are poorly understood, but are of clear relevance to mental health.

描述（由申请人提供）：血管活性肠多肽（VIP）是脊椎动物中催乳素分泌的主要调节剂，因此，即使仅通过其对催乳素的影响，也是促进父母护理中心的重要促进者。 VIP受体和纤维在所有大脑区域的高密度都发现，这些区域已知会导致父母护理，并且在整个社会行为环境中都更加一般。除了假设对父母行为的影响外，还有很多理由可以期望VIP电路还会影响侵略性行为，社会性，性行为和配对。以及动机和焦虑的更一般方面。鉴于1）斑马雀（Taeniopygia guttata）表现出非凡的可靠，可量化的行为，而2）有几种雌激素在物种上表现出很大的差异在行为和生态学的大多数其他方面，群体的大小仍然与斑马雀科密切相匹配。芬奇（Finches）的最新发现表明，群体规模的选择是独立于简单的隶属关系而滴定的，这表明存在重要但在很大程度上没有探索的社会性神经机制。社交焦虑和戒断通常与各种精神疾病和心理问题一起观察到，因此该提案将探索可能对健康的社会行为至关重要的神经行为机制，并确定可能使人们避免社会避免的变化。鸟类和哺乳动物中的边缘 - 高层丘脑回路是强烈保守的，从而使雀科的行为鲁棒性可以为哺乳动物的相关研究提供信息。 具体目标1将使用反义寡核苷酸对VIP受体的中心对抗和VIP产生的特定地点敲低，以检查男性和女性斑马雀科对社会，焦虑，筑巢和父母护理的影响。焦点观察还将在菌落环境中进行，以量化20多种行为，包括配对键。特定的目标2将在高度领土紫罗兰的Waxbill（uraeginthus granatina）中采用类似的操纵来测试侵略性和焦虑行为。具体目标3将采用合并的方案进行原位杂交和免疫细胞化学来确定哪些贵宾细胞组显示出对响应1）男性和女性斑马雀的筑巢的FOS激活增加，2）男性斑马雀的求爱，3）紫罗兰呼吸的蜡像中的积极互动和非社会防御。最后，具体目标4将1）检查在三种群居和两个领土物种中暴露于同性刺激后的VIP细胞基团的FOS激活，以及2）定量比较了同一动物中VIP mRNA的分布。侧隔隔膜中的VIP结合位点的密度与这些物种的社会性呈正相关，这表明VIP在区分群体和相对社会动物的行为和/或生理反应中可能起重要作用。这样的过程知之甚少，但与心理健康有明确的相关性。