New perspectives on vasoactive intestinal polypeptide as a widespread modulator of social behavior

Abstract

In terms of reproductive and social functions, vasoactive intestinal polypeptide (VIP) is best known as a major regulator of prolactin secretion in vertebrates and hence, as an essential contributor to parental care. However, VIP and its cognate VPAC receptors are distributed throughout the social behavior network in the brain, suggesting that VIP circuits may play important roles in a variety of behaviors. With the exception of VIP neuronal populations in the suprachiasmatic nucleus and tuberal hypothalamus (which regulate circadian rhythms and prolactin secretion, respectively), we have known very little about the functional properties of VIP circuits until recently. The present review highlights new roles for VIP signaling in avian social behaviors such as affiliation, gregariousness, pair bonding and aggression, and discusses recent advances in VIP's role as a regulator of biological rhythms, including the potential timing of ovulation, photoperiodic response and seasonal migration.

Fig. 1

VPAC antagonism alters social contact in a novel environment, gregariousness and pair bonding in zebra finches. (a) Our choice test apparatus consists of a 1 M wide testing cage subdivided into zones by seven perches with stimulus cages containing either two or ten familiar same-sex conspecifics at either end. The percent of test time spent on the two end perches combined (within 6 cm of a stimulus cage) provides a measure of “social contact time”. The percent of social contact time spent with the large group provides a measure of “gregariousness” (group size preference). (b) Ventricular VPAC antagonist infusions decrease social contact time in the choice apparatus (shown in a) on the first test day when the testing paradigm is novel, but not on the second test day. (c, d) VPAC antagonism has site- and sex-specific effects on gregariousness in choice tests. (c) A significant interaction of Sex and Treatment is observed following ICV antagonist infusions whereby VPAC antagonism tends to decrease gregariousness in females and increase it in males. (d) A main effect of Treatment is observed following VPAC antagonist infusions into the telecephalon whereby VPAC antagonism reduces gregariousness in both males and females. (a-d), modified from [36]. (e) A 1 M wide cage showing the standard setup for colony observations, with a single nest cup in each of the 4 corners, and a food dish, water sipper and burlap nesting material placed on the cage floor. Modified from Kelly and Goodson [41]. (f) Chronic VPAC receptor antagonism significantly decreases the percentage of zebra finches that are paired in the final behavioral session, as compared to control animals. Blue bars denote male values and red bars denote female values. Modified from [45].

Fig. 2

Knockdown of VIP peptide in the dorsal anterior hypothalamus (AHd) greatly reduces aggression in territorial and gregarious finches. (a) VIP elements in the hypothalamic region of the zebra finch. TH-ir, tyrosine hydroxylase immunoreactivity (-ir) (purple); NPY-ir, neuropeptide Y-ir (red); VIP-ir, vasoactive intestinal polypeptide-ir (green). Scale bar, 200 μm. (b) The AHd region is defined by a distinct VIP cell group, shown here for a violet-eared waxbill. VIP-ir, vasoactive intestinal polypeptide immunoreactivity (red); VT-ir, vasotocin-ir (green); DAPI nuclear stain (purple). Green asterisk shows site of cannula tip for VIP antisense or scrambled oligonucleotide infusions. Scale bar, 100 μm. AC, anterior commissure; AHd and AHv, anterior hypothalamus, dorsal and ventral; ME, median eminence; ot, optic tract; PVN, paraventricular nucleus; VMH-lat and VHM-med, ventral medial hypothalamus, lateral and medial. (c, d) Compared to control (scrambled) infusions, VIP antisense infusions significantly increase the latency to displace an intruder (c) and eliminate aggressive displacements in most male and female violet-eared waxbills during a resident-intruder test (d). **P = 0.01. (e) VIP Antisense infusions in male zebra finches significantly reduce aggressive behaviors in the context of nest defense within a colony environment. Males were placed into either high aggression (black bars) and low aggression (white bars) colony cages based on aggressive behavior during pre-screenings. *P = 0.02, main effect of Treatment. Modified from [53].