Previous comparisons of territorial and gregarious finches (family Estrildidae) suggest the hypothesis that arginine vasotocin (VT) neurons in the medial bed nucleus of the stria terminalis (BSTm) and V 1a -like receptors in the lateral septum (LS) promote flocking behavior. Consistent with this hypothesis, we now show that intraseptal infusions of a V 1a antagonist in male zebra finches (Taeniopygia guttata) reduce gregariousness (preference for a group of 10 versus 2 conspecific males), but have no effect on the amount of time that subjects spend in close proximity to other birds ("contact time"). The antagonist also produces a profound increase in anxiety-like behavior, as exhibited by an increased latency to feed in a novelty-suppressed feeding test. Bilateral knockdown of VT production in the BSTm using LNA-modified antisense oligonucleotides likewise produces increases in anxiety-like behavior and a potent reduction in gregariousness, relative to subjects receiving scrambled oligonucleotides. The antisense oligonucleotides also produced a modest increase in contact time (irrespective of group size). Together, these combined experiments provide clear evidence that endogenous VT promotes preferences for larger flock sizes, and does so in a manner that is coupled to general anxiolysis. Given that homologous peptide circuitry of the BSTm-LS is found across all tetrapod vertebrate classes, these findings may be predictive for other highly gregarious species.Central nonapeptide circuits play phylogenetically widespread roles in the modulation of social behaviors and stress responses and often exert their effects in a species-specific manner (Engelmann et al., 2004;De Vries and Panzica, 2006;Donaldson and Young, 2008;Veenema and Neumann, 2008;Choleris et al., 2009;Goodson and Thompson, 2010). These circuits arise primarily from magnocellular and parvocellular neurons in the preoptic area and hypothalamus that produce either arginine vasotocin (VT; in nonmammalian vertebrates) or arginine vasopressin (VP; in mammals), plus a single oxytocin-like peptide form in any given species. In addition to these cell groups, virtually all tetrapods, including humans, exhibit VT/VP neurons in the medial extended amygdala, primarily within the medial bed nucleus of the stria terminalis (BSTm) (De Vries and Panzica, 2006;Goodson and Thompson, 2010). Unlike the various hypothalamic VT/VP cell groups, the BSTm neurons and their projections to basal forebrain sites such as the lateral septum (LS), medial preoptic area and habenula Absil et al., 2002) are typically sexually

We have previously demonstrated that centrally administered vasotocin (VT) inhibits social approach toward same-sex conspecifics in male and female goldfish, and that this behavioral effect is dependent upon VT projections to the hindbrain. We now show that there are no sex differences in sensitivity to the behavioral effects of VT, though differences do exist in responsiveness across seasons in both sexes. A central dose of 1 µg, but not 200 ng, inhibited social approach in goldfish in non-reproductive condition, whereas a dose as low as 40 ng inhibited social approach in fish in full reproductive condition. In males and females in full reproductive condition, social approach behavior was facilitated by central administration of 500 ng of a V1A specific antagonist. In addition, the behavioral effects of exogenously administered central VT were blocked by central administration of 1 µg of a V1A antagonist. These results demonstrate that the propensity to approach a conspecific, a simple behavior underlying many social interactions, is controlled by a V1A-like receptor, and that VT’s behavioral effects depend on reproductive context. Quantitative real-time PCR showed that the seasonal changes in behavioral responsiveness to VT are associated with changes in the expression of a V1A-like receptor in the hindbrain, but not the mid- or forebrain, indicating that the seasonal regulation of social approach behavior likely depends on the local modulation of the expression of this receptor within a primitive peptide circuit in this species.