VPAC receptor signaling modulates grouping behavior and social responses to contextual novelty in a gregarious finch: A role for a putative prefrontal cortex homologue

In both mammals and birds, vasoactive intestinal polypeptide (VIP) neurons and fibers are present in virtually every brain area that is important for social behavior. VIP influences aggression in birds, social recognition in rodents, and prolactin secretion in both taxa, but other possible functions in social modulation remain little explored. VIP effects are mediated by VPAC receptors, which bind both VIP and pituitary adenylate cyclase activating peptide. Within the lateral septum and medial bed nucleus of the stria terminalis, VPAC receptors are found at higher densities in gregarious finch species relative to territorial species, suggesting that VPAC receptor activation promotes social contact and/or preference for larger groups. Here we here test this hypothesis in zebra finches (Taeniopygia guttata), and also examine the relevance of VPAC receptors to anxiety-like processes. Intraventricular infusions of the VPAC receptor antagonist, neurotensin6–11 mouseVIP7–28, strongly reduce social contact when animals are tested in a novel environment, and exert sex-specific effects on grouping behavior. Specifically, VPAC receptor antagonism reduces gregariousness in females but increases gregariousness in males. Interestingly, VPAC antagonism in the medial pallium (putative prefrontal cortex homologue) significantly reduces gregariousness in both sexes, suggesting site-specific effects of VIP signaling. However, VPAC antagonism does not modulate novel-familiar social preferences in a familiar environment or general anxiety-like behaviors. The current results suggest that endogenous activation of VPAC receptors promotes social contact under novel environmental conditions, a function that may be accentuated in gregarious species. Moreover, endogenous VIP modulates gregariousness in both males and females.     

Dynamic neuromodulation of aggression by vasotocin: influence of social context and social phenotype in territorial songbirds

The homologous neuropeptides vasotocin (VT) and vasopressin (VP) influence agonistic behaviours across many taxa, but peptide–behaviour relationships are complex and purportedly species-specific. Putative species-specific effects in songbirds are confounded with context, however, such that territorial species have been tested only in resident–intruder paradigms and gregarious species have been tested only in a mate competition paradigm. Using the territorial violet-eared waxbill (Estrildidae: Uraeginthus granatina), we now show that a V_1a receptor antagonist reduces male aggression during mate competition (as in gregarious finches), but does not affect resident–intruder aggression in dominant males. However, the V_1a antagonist disinhibits aggression in less aggressive (typically subordinate) males. These results are consistent with recent data on the activation of different VT cell groups during positive and negative social interactions. Thus, VT influences aggression similarly across territorial and gregarious species, but in context- and phenotype-specific ways that probably reflect the differential activation of discrete VT cell groups.     

Vasotocin neurons in the bed nucleus of the stria terminalis preferentially process social information and exhibit properties that dichotomize courting and non-courting phenotypes

Neurons within the medial bed nucleus of the stria terminalis (BSTm) that produce arginine vasotocin (VT; in non-mammals) or arginine vasopressin (VP; in mammals) have been intensively studied with respect to their anatomy and neuroendocrine regulation. However, almost no studies have examined how these neurons process stimuli in the animals' immediate environment. We recently showed that in five estrildid finch species, VT-immunoreactive (-ir) neurons in the BSTm increase their Fos expression selectively in response to positively-valenced social stimuli (i.e., stimuli that should elicit affiliation). Using male zebra finches, a highly gregarious estrildid, we now extend those findings to show that VT-Fos coexpression is induced by a positive social stimulus (a female), but not by a positive non-social stimulus (a water bath in bath-deprived birds), although the female and bath stimuli induced Fos equally within a nearby control region, the medial preoptic nucleus. In concurrent experiments, we also show that the properties of BSTm VT-ir neurons strongly differentiate males that diverge in social phenotype. Males who reliably fail to court females (“non-courters”) have dramatically fewer VT-ir neurons in the BSTm than do reliable courters, and the VT-ir neurons of non-courters fail to exhibit Fos induction in response to a female stimulus.     

Sex-specific activity and function of hypothalamic nonapeptide neurons during nest-building in zebra finches

Vertebrate species from fish to humans engage in a complex set of preparatory behaviors referred to as nesting; yet despite its phylogenetic ubiquity, the physiological and neural mechanisms that underlie nesting are not well known. We here test the hypothesis that nesting behavior is influenced by the vasopressin–oxytocin (VP–OT) peptides, based upon the roles they play in parental behavior in mammals. We quantified nesting behavior in male and female zebra finches following both peripheral and central administrations of OT and V_1a receptor (OTR and V1aR, respectively) antagonists. Peripheral injections of the OTR antagonist profoundly reduce nesting behavior in females, but not males, whereas comparable injections of V1aR antagonist produce relatively modest effects in both sexes. However, central antagonist infusions produce no effects on nesting, and OTR antagonist injections into the breast produce significantly weaker effects than those into the inguinal area, suggesting that antagonist effects are mediated peripherally, likely via the oviduct. Finally, immunocytochemistry was used to quantify nesting-induced Fos activation of nonapeptide neurons in the paraventricular and supraoptic nuclei of the hypothalamus and the medial bed nucleus of the stria terminalis. Nest-building induced Fos expression within paraventricular VP neurons of females but not males. Because the avian forms of OT (Ile⁸-OT; mesotocin) and VP (Ile³-VP; vasotocin) exhibit high affinity for the avian OTR, and because both peptide forms modulate uterine contractility, we hypothesize that nesting-related stimuli induce peptide release from paraventricular vasotocin neurons, which then promote female nesting via peripheral feedback from OTR binding in the oviduct uterus.     

Competitive interactions between parasitoid larvae and the evolution of gregarious development

We report experiments using two closely related species of alysiine braconids directed at understanding how gregarious development evolved in one subfamily of parasitoid wasps. Theoretical models predict that once siblicide between parasitoid wasps has evolved, it can only be lost under stringent conditions, making the transition from solitary to gregarious development exiguous. Phylogenetic studies indicate, however, that gregariousness has independently arisen on numerous occasions. New theoretical models have demonstrated that if gregarious development involves reductions in larval mobility, rather than a lack of fighting ability (as in the older models), the evolution of gregariousness is much more likely. We tested the predictions of the older tolerance models (gregariousness based on non-fighting larval phenotypes) and the reduced mobility models (gregariousness based on non-searching larval phenotypes) by observing larval movement and the outcome of interspecific competition between Aphaereta genevensis (solitary) and A. pallipes (gregarious) under multiparasitism. Differences in larval mobility matched the prediction of the reduced mobility model of gregarious development, with the solitary A. genevensis having larvae that are much more mobile. The proportion of hosts producing the solitary species significantly declined after subsequent exposure to females of the gregarious species. This contradicts the prediction of the older models (fighting vs non-fighting phenotypes), under which any competitive interactions between solitary and gregarious larvae will result in a highly asymmetrical outcome, as the solitary species should be competitively superior. The observed outcome of interspecific competition offers evidence, with respect to this subfamily, in favour of the new models (searching vs non-searching phenotypes).     

Effects of central vasotocin and mesotocin manipulations on social behavior in male and female zebra finches

Male and female zebra finches (Taeniopygia guttata; total n = 40) were fitted with chronic guide cannulae directed at the lateral ventricle and were tested for aggression, affiliation, and partner preference following infusions of mesotocin (MT), vasotocin (VT), their antagonists, and vehicle control. Aggressive behavior was tested in a mate competition paradigm and tests of intersexual affiliation and partner preference were conducted following 1 day of cohabitation with an opposite-sex individual. These tests also provided data on male courtship singing. The results demonstrate a modest dose-dependent facilitation of aggression by VT, but not MT, in both male and female finches. However, only males were sensitive to infusions of a vasopressin antagonist, suggesting that endogenous VT is more important for behavioral modulation in males. Peptide effects were specific to aggression, as no treatments influenced intersexual affiliation, partner preference, or male courtship singing. Thus, in contrast to rodents, partner preference is not readily induced by VT or MT in this species. However, the potential necessity of endogenous VT and MT for natural pair-bond formation remains to be tested.     

Linking spatial processes to life-history evolution of insect parasitoids

Understanding the evolutionary transition from solitary to group living in animals is a profound challenge to evolutionary ecologists. A special case is found in insect parasitoids, where a tolerant gregarious larval lifestyle evolved from an intolerant solitary ancestor. The conditions for this transition are generally considered to be very stringent. Recent studies have aimed to identify conditions that facilitate the spread of a gregarious mutant. However, until now, ecological factors have not been included. Host distributions and life-history trade-offs affect the distribution of parasitoids in space and thus should determine the evolution of gregariousness. We add to current theory by using deterministic models to analyze the role of these ecological factors in the evolution of gregariousness. Our results show that gregariousness is facilitated through inversely density-dependent patch exploitation. In contrast, host density dependence in parasitoid distribution and patch exploitation impedes gregariousness. Numerical solutions show that an aggressive gregarious form can more easily invade a solitary population than can a tolerant form. Solitary forms can more easily invade a gregarious, tolerant population than vice versa. We discuss our results in light of exploitation of multitrophic chemical cues by searching parasitoids and aggregative and defensive behavior in herbivorous hosts.     

The role of larval aggression and mobility in the transition between solitary and gregarious development in parasitoid wasps

Models explaining the appearance of gregariousness in insect parasitoids assume the presence of a tolerance gene that enables nonsiblicidal behaviour in gregarious larvae. Under this assumption, nontolerant individuals should attack and kill tolerant individuals when sharing a host, making this behaviour susceptible to invasion by nontolerant individuals. We propose an alternative hypothesis where gregarious larvae retain their aggressiveness but are less mobile. We tested this hypothesis with two sympatric and congeneric species of Mymaridae, Anaphes victus and Anaphes listronoti , respectively, solitary and gregarious egg parasitoids of a Curculionidae, Listronotus oregonensis . Results obtained in competition experiments and from direct observation of movement in mymariform larvae of both species support the reduced mobility hypothesis. By being immobile while retaining their fighting capacity, A. listronoti mymariform larvae appear to optimize host utilization through gregarious development, but can still defend themselves against sympatric aggressive species.     

Neuropeptide binding reflects convergent and divergent evolution in species-typical group sizes

Neuroendocrine factors that produce species differences in aggregation behavior ("sociality") are largely unknown, although relevant studies should yield important insights into mechanisms of affiliation and social evolution. We here focused on five species in the avian family Estrildidae that differ selectively in their species-typical group sizes (all species are monogamous and occupy similar habitats). These include two highly gregarious species that independently evolved coloniality; two territorial species that independently evolved territoriality; and an intermediate, modestly gregarious species that is a sympatric congener of one of the territorial species. Using males and females of each species, we examined binding sites for (125)I-vasoactive intestinal polypeptide (VIP), (125)I-sauvagine (SG; a ligand for corticotropin releasing factor, CRF, receptors) and a linear (125)I-V(1a) vasopressin antagonist (to localize receptors for vasotocin, VT). VIP, CRF and VT are neuropeptides that influence stress, anxiety and/or various social behaviors. For numerous areas (particularly within the septal complex), binding densities in the territorial species differed significantly from binding in the more gregarious species, and in most of these cases, binding densities for the moderately gregarious species were either comparable to the two colonial species or were intermediate to the territorial and colonial species. Such patterns were observed for (125)I-VIP binding in the medial bed nucleus of the stria terminalis, medial septum, septohippocampal septum, and subpallial zones of the lateral septum; for (125)I-SG binding in the infundibular hypothalamus, and lateral and medial divisions of the ventromedial hypothalamus; and for the linear (125)I-V(1a) antagonist in the medial septum, and the pallial and subpallial zones of the caudal lateral septum. With the exception of (125)I-SG binding in the infundibular hypothalamus, binding densitites are positively related to sociality.     

Neuroendocrine correlates of behavioral polymorphism in white-throated sparrows

Interspecific differences in the neuropeptide systems of the lateral septum (LS) often parallel differences in social behavior. In rodents, some closely related species that differ in aggressive behavior also differ according to the level of vasopressin (VP) innervation of the LS. In songbirds, the neuropeptides vasotocin (VT) and vasoactive intestinal peptide (VIP) affect aggression when administered directly to the LS. Here, we tested whether the density of VT or VIP innervation of the LS reflects patterns of intraspecific behavioral polymorphism in male and female white-throated sparrows (Zonotrichia albicollis), in which the "white-stripe" (WS) morph behaves more aggressively than the "tan-stripe" (TS) morph. We found that the WS birds had more VT-immunoreactivity (IR) than the TS birds in the ventrolateral subdivision of the caudal LS (LSc.vl) and in the medial portion of the bed nucleus of the stria terminalis (BSTm). In addition, the TS birds had more densely stained VIP-IR in the LSc.vl than the WS birds. Males had more VT-IR than females in the LSc.vl and BSTm, and more VIP-IR in the LSc.vl. We also report sex and morph differences in VIP-IR in the basal hypothalamus, where VIP is synthesized and released into the portal vasculature. Males had nearly twice as many VIP-immunoreactive (ir) neurons in the infundibular nucleus than did females, and birds of the WS morph had more densely stained VIP-IR in the median eminence than TS birds. Our results support the hypothesis that differences in these neuropeptide systems underlie inter- and intraspecific differences in social behavior across vertebrates.     

Antagonistic effects of vasotocin and isotocin on the upper esophageal sphincter muscle of the eel acclimated to seawater

The effects of isotocin (IT) and vasotocin (VT), which are fish analogues of mammalian oxytocin and vasopressin respectively, were examined in the isolated upper esophageal sphincter (UES) muscle. IT relaxed and VT constricted the UES muscle in a concentration-dependent manner. The relaxation by IT and the contraction by VT were completely blocked by H-9405 (an oxytocin receptor antagonist) and by H-5350 (a V₁-receptor antagonist), respectively, suggesting that the eel UES possesses both IT and VT receptors. Truncated fragments of VT did not show any significant effects, indicating that all nine residues are essential for the VT and IT actions. IT may relax the UES muscle through enhancing cAMP production, since similar relaxation was also observed after treatment with 3-isobutyl-1-methylxantine, forskolin and 8-bromoadenosine, 3′, 5′-cyclic mono-phosphate (8BrcAMP). Although 8-bromoguanosine, 3′, 5′-cyclic monophosphate also relaxed the UES, its effect was less than 1/3 of that 8BrcAMP, suggesting minor contribution of nitric oxide (NO) in the relaxation of the UES muscle. Both peptides seem to act directly on the UES muscle, not through release of other substances from the epithelial cells, since similar relaxation and contraction were observed even in the scraped UES preparations. When IT and VT were intravenously administrated (in vivo experiments), the drinking rate of the seawater eel was enhanced by IT and was inhibited by VT. These effects correspond to the in vitro results described above, relaxation by IT and contraction by VT in the UES muscle. The significance of the relaxing effect by IT is discussed with respect to controlling the drinking behavior of the eel.     

Endogenous vasotocin exerts context-dependent behavioral effects in a semi-naturalistic colony environment

Arginine vasotocin (VT), and its mammalian homologue arginine vasopressin (VP), are neuropeptides involved in the regulation of social behaviors and stress responsiveness. Previous research has demonstrated opposing effects of VT/VP on aggression in different species. However, these divergent effects were obtained in different social contexts, leading to the hypothesis that different populations of VT/VP neurons regulate behaviors in a context-dependent manner. We here use VP antagonists to block endogenous VT function in male zebra finches (Taeniopygia guttata) within a semi-natural, mixed-sex colony setting. We examine the role of VT in the regulation of aggression and courtship, and in pair bond formation and maintenance, over the course of three days. Although our results confirm previous findings, in that antagonist treatment reduces aggressive mate competition during an initial behavioral session during which males encounter novel females, we find that the treatment effects are completely reversed within hours of colony establishment, and the antagonist treatment instead facilitates aggression in later sessions. This reversal occurs as aggression shifts from mate competition to nest defense, but is not causally associated with pairing status per se. Instead, we hypothesize that these divergent effects reflect context-specific activation of hypothalamic and amygdalar VT neurons that exert opposing influences on aggression. Across contexts, effects were highly specific to aggression and the antagonist treatment clearly failed to alter latency to pair bond formation, pair bond stability, and courtship. However, VT may still potentially influence these behaviors via promiscuous oxytocin-like receptors, which are widely distributed in the zebra finch brain.     

Maternal care, defensive behavior, and sociality in neotropical Goniosoma harvestmen (Arachnida, Opiliones)

Summary: Goniosoma includes large and conspicuous species of harvestmen that occur exclusively in the Brazilian Atlantic forest. This paper reports on the parental activities, defensive behavior, and gregariousness of five species of Goniosoma, and also summarizes the published biological data for the genus. The behavioral patterns within the genus are discussed and a hypothesis for the emergence of gregariousness in the group is presented. Several Goniosoma live inside caves, mainly as trogloxenes. Although species of the genus comprise only 5% of the harvestmen fauna in Brazil, they account for 20.6% of all harvestmen species recorded in Brazilian caves. In addition to several morphological and physiological features that may favor the occupation of caves, species of Goniosoma also present subsocial behavior, which may confer a special advantage in this particular environment. Female protection is crucial for egg survival since predators may consume entire batches in a single night. Most species of Goniosoma form dense diurnal aggregations ranging from three to 200 individuals (mainly subadults and adults of both sexes). In a hypothetical scenario for the evolution of sociality in the Goniosoma, physiological constraints acting on individual harvestmen would lead to a behavioral response for the selection of sites with appropriate microclimatic conditions. The lack of cannibalism among adults and subadults may favor tolerance towards conspecifics, and may represent a pre-adaptation to gregariousness. The derived functions of gregarious behavior may include strengthening of the defensive signal through the collective release of a repugnant secretion, the dilution effect, and promptness in fleeing a predator attack as a consequence of the additional alarm role of scent gland secretions. These defensive functions may overcome the costs of group living and may be responsible for the maintenance of gregariousness in Goniosoma.     

Gregarious settlement in cypris larvae:the effects of cyprid age and assay duration

Gregarious behaviour of marine larvae is perhaps most clearly associated with finding a suitable habitat in a changeable or restricted environment, or with finding other conspecifics with which to mate. Prior work has shown that in settlement assays using cypris larvae of the barnacle Balanus amphitrite, gregarious interactions significantly affected the interpretation of experiments testing the activity of organic settlement promoters and inhibitors. Other studies have also shown effects of cyprid age and pheromone concentration on settlement behaviour. However, the effects of interactions between gregariousness and these two factors are not known. The aim of this study was to test the hypotheses that i) as cyprids age the effects of gregariousness become less apparent, and ii) as the duration of the experiment increases gregarious effects become more apparent, using cypris larvae of B. amphitrite and Balanus improvisus. Three age classes of cyprids were used at six densities in a fully factorial design. For B. improvisus cyprids significant gregarious effects occurred between 3 or more larvae, and although larval age and experiment duration had significant main effects, there were no interactions between these important factors and gregariousness. For B. amphitrite cyprids significant gregarious effects also occurred with 3 larvae per well, though this effect was strongly dependent upon experiment duration. B. amphitrite cyprid sensitivity to conspecific cues does not change with age, although increasing experiment duration and age interact to increase settlement. Differences between species may be due to different thresholds to conspecific larval cues, or B. improvisus cyprids release much more larval temporary adhesive during exploration.     

How feeding competition determines female chimpanzee gregariousness and ranging in the Taï National Park, Côte d'Ivoire

Socioecological theory suggests that feeding competition shapes female social relationships. Chimpanzees (Pan troglodytes) live in fission–fusion societies that allow them to react flexibly to increased feeding competition by forming smaller foraging parties when food is scarce. In chimpanzees at Gombe and Kibale, female dominance rank can crucially influence feeding competition and reproductive success as high‐ranking females monopolize core areas of relatively high quality, are more gregarious, and have higher body mass and reproductive success than low‐ranking females. Chimpanzee females in Taï National Park do not monopolize core areas; they use the entire territory as do the males of their community and are highly gregarious. Although female chimpanzees in Taï generally exhibit a linear dominance hierarchy benefits of high rank are currently not well understood. We used a multivariate analysis of long‐term data from two Taï chimpanzee communities to test whether high‐ranking females (1) increase gregariousness and (2) minimize their travel costs. We found that high‐ranking females were more gregarious than low‐rankers only when food was scarce. During periods of food scarcity, high rank allowed females to enjoy benefits of gregariousness, while low‐ranking females strongly decreased their gregariousness. High‐ranking females traveled more than low‐ranking females, suggesting that low‐rankers might follow a strategy to minimize energy expenditure. Our results suggest that, in contrast to other chimpanzee populations and depending on the prevailing ecological conditions, female chimpanzees at Taï respond differently to varying levels of feeding competition. Care needs to be taken before generalizing results found in any one chimpanzee population to the species level. Am. J. Primatol. 73:305–313, 2011. © 2010 Wiley‐Liss, Inc.     

Synthesis and evaluation of azabicyclo[3.2.1]octane derivatives as potent mixed vasopressin antagonists

A series of biaryl amides containing an azabicyclooctane amine headpiece were synthesized and evaluated as mixed arginine vasopressin (AVP) receptor antagonists. Several analogues, including 8g, 12g, 13d, and 13g, were shown to have excellent V_1a- and good V₂-receptor binding affinities. Compound 13d was further profiled for drug-like properties and for an in vitro comparison with conivaptan, the program’s mixed V_1a/V₂-receptor antagonist standard.     

Oligonucleotides conjugated with short chemically defined polyethylene glycol chains are efficient antisense agents

Ligand conjugation is an attractive approach to rationally modify the poor pharmacokinetic behavior and cellular uptake properties of antisense oligonucleotides. Polyethylene glycol (PEG) attachment is a method to increase solubility of oligonucleotides and prevent the rapid elimination, thus increasing tissue distribution. On the other hand, the attachment of long PEG chains negatively influences the pharmacodynamic effect by reducing the hybridization efficiency. We examined the use of short PEG ligands on the in vitro effect of antisense agents. Circular dichroism showed that the tethering of PEG₁₂-chains to phosphodiester and phosphorothioate oligonucleotides had no influence on their secondary structure and did not reduce the affinity to the counter strand. In an in vitro tumor model, a luciferase reporter assay indicated unchanged gene silencing activity compared to unmodified compounds, and even slightly superior target down regulation was found after treatment with a phosphorothioate modified conjugate.