Social and Motivational Properties of Vasoactive Intestinal Polypeptide Circuits

Trustees Of Indiana University, Bloomington IN

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Abstract

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.