Partner separation rescues pair bond-induced decreases in hypothalamic oxytocin neural densities.

Studies in prairie voles (Microtus ochrogaster) have shown that although formation of the pair bond is accompanied by a suite of behavioral changes, a bond between two voles can dissolve and individuals can form new pair bonds with other conspecifics. However, the neural mechanisms underlying this behavioral flexibility have not been well-studied. Here we examine plasticity of nonapeptide, vasopressin (VP) and oxytocin (OT), neuronal populations in relation to bonding and the dissolution of bonds. Using adult male and female prairie voles, animals were either pair bonded, co-housed with a same-sex sibling, separated from their pair bond partner, or separated from their sibling. We examined neural densities of VP and OT cell groups and observed plasticity in the nonapeptide populations of the paraventricular nucleus of the hypothalamus (PVN). Voles that were pair bonded had fewer PVN OT neurons, suggesting that PVN OT neural densities decrease with pair bonding, but increase and return to a pre-pair bonded baseline after the dissolution of a pair bond. Our findings suggest that the PVN nonapeptide cell groups are particularly plastic in adulthood, providing a mechanism by which voles can exhibit context-appropriate behavior related to bond status.

Hypothalamic oxytocin and vasopressin neurons exert sex-specific effects on pair bonding, gregariousness, and aggression in finches.

Antagonism of oxytocin (OT) receptors (OTRs) impairs the formation of pair bonds in prairie voles (Microtus ochrogaster) and zebra finches (Taenioypygia guttata), and also reduces the preference for the larger of two groups ("gregariousness") in finches. These effects tend to be stronger in females. The contributions of specific peptide cell groups to these processes remain unknown, however. This issue is complicated by the fact that OTRs in finches and voles bind not only forms of OT, but also vasopressin (VP), and >10 cell groups produce each peptide in any given species. Using RNA interference, we found that knockdown of VP and OT production in the paraventricular nucleus of the hypothalamus exerts diverse behavioral effects in zebra finches, most of which are sexually differentiated. Our data show that knockdown of VP production significantly reduces gregariousness in both sexes and exerts sex-specific effects on aggression directed toward opposite-sex birds (increases in males; decreases in females), whereas OT knockdown produces female-specific deficits in gregariousness, pair bonding, and nest cup ownership; reduces side-by-side perching in both sexes; modulates stress coping; and induces hyperphagia in males. These findings demonstrate that paraventricular neurons are major contributors to the effects of VP-OT peptides on pair bonding and gregariousness; reveal previously unknown effects of sex-specific peptide on opposite-sex aggression; and demonstrate a surprising lack of effects on same-sex aggression. Finally, the observed effects of OT knockdown on feeding and stress coping parallel findings in mammals, suggesting that OT modulation of these processes is evolutionarily conserved across the amniote vertebrate classes.

An aggression-specific cell type in the anterior hypothalamus of finches.

The anterior hypothalamus (AH) is a major integrator of neural processes related to aggression and defense, but cell types in the AH that selectively promote aggression are unknown. We here show that aggression is promoted in a very selective and potent manner by dorsal AH neurons that produce vasoactive intestinal polypeptide (VIP). Fos activity in a territorial finch, the violet-eared waxbill (Estrildidae: Uraeginthus granatina) is positively related to aggression in the dorsal AH, overlapping a population of VIP-producing neurons. VIP is known to promote territorial aggression in songbirds, and thus we used antisense oligonucleotides to selectively block AH VIP production in male and female waxbills. This manipulation virtually abolishes aggression, reducing the median number of displacements in a 3-min resident-intruder test from 38 in control subjects to 0 in antisense subjects. Notably, most antisense and control waxbills exhibit an agonistic response such as a threat or agonistic call within 2 s of intrusion. Thus, antisense subjects clearly classify intruders as offensive, but fail to attack. Other social and anxiety-like behaviors are not affected and VIP cell numbers correlate positively with aggression, suggesting that these cells selectively titrate aggression. Additional experiments in the gregarious zebra finch (Estrildidae: Taeniopygia guttata) underscore this functional specificity. Colony-housed finches exhibit significant reductions in aggression (primarily nest defense) following AH VIP knockdown, but no effects are observed for social preferences, pair bonding, courtship, maintenance behaviors, or anxiety-like behaviors. To our knowledge, these findings represent a unique identification of an aggression-specific cell type in the brain.

Dopaminergic regulation of mate competition aggression and aromatase-Fos colocalization in vasotocin neurons.

Recent experiments demonstrate that aggressive competition for potential mates involves different neural mechanisms than does territorial, resident-intruder aggression. However, despite the obvious importance of mate competition aggression, we know little about its regulation. Immediate early gene experiments show that in contrast to territorial aggression, mate competition in finches is accompanied by the activation of neural populations associated with affiliation and motivation, including vasotocin (VT) neurons in the medial bed nucleus of the stria terminalis (BSTm) and midbrain dopamine (DA) neurons that project to the BSTm. Although VT is known to facilitate mate competition aggression, the role of DA has not previously been examined. We now show that in male zebra finches (Taeniopygia guttata), mate competition aggression is inhibited by the D(2) agonist quinpirole, though not the D(1) agonist SKF-38393 or the D(4) agonist PD168077. The D(3) agonist 7-OH-DPAT also inhibited aggression, but only following high dose treatment that may affect aggression via nonspecific binding to D(2) receptors. Central VT infusion failed to restore D(2) agonist-inhibited aggression in a subsequent experiment, demonstrating that D(2) does not suppress aggression by inhibiting VT release from BSTm neurons. In a final experiment, we detected D(2) agonist-induced increases in immunofluorescent colocalization of the product of the immediate early gene c-fos and the steroid-converting enzyme aromatase (ARO) within VT neurons of the BSTm. Thus, although VT and DA appear to influence mate competition aggression independently, BSTm VT neurons are clearly influenced by the activation of D(2) receptors, which may modify future behaviors.