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The bed nucleus of the stria terminalis (BNST) has been implicated in a variety of social behaviors, including aggression, maternal care, mating behavior, and social interaction. Limited evidence from rodent studies suggests that activation of the BNST results in a decrease in social interaction between unfamiliar animals. The role of the BNST in social interaction in primates remains wholly unexamined. Nonhuman primates provide a valuable model for studying social behavior because of both their rich social repertoire and neural substrates of behavior with high translational relevance to humans. To test the hypothesis that the primate BNST is a critical modulator of social behavior, we performed intracerebral microinfusions of the GABAA agonist muscimol to transiently inactivate the BNST in male macaque monkeys. We measured changes in social interaction with a familiar same-sex conspecific. Inactivation of the BNST resulted in significant increase in total social contact. This effect was associated with an increase in passive contact and a significant decrease in locomotion. Other nonsocial behaviors (sitting passively alone, self-directed behaviors, and manipulation) were not impacted by BNST inactivation. As part of the "extended amygdala," the BNST is highly interconnected with the basolateral (BLA) and central (CeA) nuclei of the amygdala, both of which also play critical roles in regulating social interaction. The precise pattern of behavioral changes we observed following inactivation of the BNST partially overlaps with our prior reports in the BLA and CeA. Together, these data demonstrate that the BNST is part of a network regulating social behavior in primates. [ABSTRACT FROM AUTHOR]

Stimulation of the intermediate and deep layers of superior colliculus (DLSC) in rodents evokes both orienting/pursuit (approach) and avoidance/flight (defense) responses (Dean et al., 1989). These two classes of response are subserved by distinct output projections associated with lateral (approach) and medial (defense) DLSC (Comoli et al., 2012). In non-human primates, DLSC has been examined only with respect to orienting/approach behaviors, especially eye movements, and defense-like behaviors have not been reported. Here we examined the profile of behavioral responses evoked by activation of DLSC by unilateral intracerebral infusions of the G AB Aa receptor antagonist, bicuculline methiodide (BIC), in nine freely moving macaques. Across animals, the most consistently evoked behavior was cowering (all animals), followed by increased vocalization and escape-like behaviors (seven animals), and attack of objects (three animals). The effects of BIC were dose-dependent within the range 2.5-14 nmol (threshold dose of 4.6 nmol). The behaviors and their latencies to onset did not vary across different infusion sites within DLSC. Cowering and escape-like behaviors resembled the defense-like responses reported after DLSC stimulation in rats, but in the macaques these responses were evoked from both medial and lateral sites within DLSC. Our findings are unexpected in the context of an earlier theoretical perspective (Dean et al., 1989) that emphasized a preferential role of the primate DLSC for approach rather than defensive responses. Our data provide the first evidence for induction of defense-like behaviors by activation of DLSC in monkeys, suggesting that the role of DLSC in responding to threats is conserved across species. [ABSTRACT FROM AUTHOR]

Cervical dystonia (CD; spasmodic torticollis) can be evoked by inhibition of substantia nigra pars reticulata (SNpr) in the nonhuman primate (Burbaud et al., 1998; Dybdal et al., 2012). Suppression of GABAergic neurons that project from SNpr results in the disinhibition of the targets to which these neurons project. It therefore should be possible to prevent CD by inhibition of the appropriate nigral target region(s). Here we tested the hypothesis that the deep and intermediate layers of the superior colliculus (DLSC), a key target of nigral projections, are required for the emergence of CD. To test this hypothesis, we pretreated the DLSC of four macaques with the GABAA agonist muscimol to determine whether this treatment would prevent CD evoked by muscimol infusions in SNpr. Our data supported this hypothesis: inhibition of DLSC attenuated CD evoked by muscimol in SNpr in all four animals. In two of the four subjects, quadrupedal rotations were evoked by muscimol application into SNpr sites that were distinct from those that induced dystonia. We found that inhibition of DLSC did not significantly alter quadrupedal rotations, suggesting that this response is dissociable from the SNpr-evoked CD. Our results are the first to demonstrate a role of DLSC in mediating the expression of CD. Furthermore, these data reveal a functional relationship between SNpr and DLSC in regulating posture and movement in the nonhuman primate, raising the possibility that the nigrotectal pathway has potential as a target for therapeutic interventions for CD. [ABSTRACT FROM AUTHOR]

The orbitofrontal cortex (OFC) and its interactions with the basolateral amygdala (BLA) are critical for goal-directed behavior, especially for adapting to changes in reward value. Here we used a reinforcer devaluation paradigm to investigate the contribution of OFC to this behavior in four macaques. Subjects that had formed associations between objects and two different primary reinforcers (foods) were presented with choices of objects overlying the two different foods. When one of the two foods was devalued by selective satiation, the subjects shifted their choices toward the objects that represented the nonsated food reward (devaluation effect). Transient inactivation of OFC by infusions of the GABAA receptor agonist muscimol into area 13 blocked the devaluation effect: the monkeys did not reduce their selection of objects associated with the devalued food. This effect was observed when OFC was inactivated during both satiation and the choice test, and during the choice test only. This supports our hypothesis that OFC activity is required during the postsatiety object choice period to guide the selection of objects. This finding sharply contrasts with the role of BLA in the same devaluation process (Wellman et al., 2005). Whereas activity in BLA was required during the selective satiation procedure, it was not necessary for guiding the subsequent object choice. Our results are the first to demonstrate that transient inactivation of OFC is sufficient to disrupt the devaluation effect, and to document a role for OFC distinct from that of BLA for the conditioned reinforcer devaluation process in monkeys. [ABSTRACT FROM AUTHOR]

Amygdala ablation disrupts reinforcer "devaluation" in monkeys (Malkova et al., 1997). Here, we tested the hypothesis that transient inactivation of amygdala by the GABAA agonist muscimol (MUS), specifically during the period of reward satiation, would have a similar effect. Six pigtail macaques were trained on a visual object discrimination task in which 60 objects were associated with one of two specific food rewards. Subsequently, we evaluated the selective satiation-induced change (devaluation) in object preference in probe sessions. We also examined the effect of the amygdala inactivation during the probe sessions to determine whether the inactivation limited to the testing period (and not during the satiation period) is sufficient to impair the expression of reinforcer devaluation. MUS infusions were aimed at basolateral amygdala (BLA) in a pseudorandomized design; each monkey received MUS or saline either before or after selective satiation with each of the two food rewards (six infusions total). Under the control (saline) condition, the monkeys significantly shifted their preference from objects representing the sated food rewards to those representing the nonsated rewards (30% change). When BLA was inactivated during selective satiation (i.e., MUS infused before satiation), this devaluation effect was blocked. In contrast, MUS infusion after satiation, so that it was present just during the testing period, did not impair the shift in object preference (27% change). Thus, BLA is necessary for the appropriate registration of the change in the reinforcer value but not for the subsequent expression of the devaluation involving its transfer to secondary reinforcers. [ABSTRACT FROM AUTHOR]