Genetic disruption of dopamine ß-hydroxylase dysregulates innate responses to predator odor in mice.

In rodents, exposure to predator odors such as cat urine acts as a severe stressor that engages innate defensive behaviors critical for survival in the wild. The neurotransmitters norepinephrine (NE) and dopamine (DA) modulate anxiety and predator odor responses, and we have shown previously that dopamine ß-hydroxylase knockout (Dbh -/-), which reduces NE and increases DA in mouse noradrenergic neurons, disrupts innate behaviors in response to mild stressors such as novelty. We examined the consequences of Dbh knockout on responses to predator odor (bobcat urine) and compared them to Dbh-competent littermate controls. Over the first 10 min of predator odor exposure, controls exhibited robust defensive burying behavior, whereas Dbh -/- mice showed high levels of grooming. Defensive burying was potently suppressed in controls by drugs that reduce NE transmission, while excessive grooming in Dbh -/- mice was blocked by DA receptor antagonism. In response to a cotton square scented with a novel "neutral" odor (lavender), most control mice shredded the material, built a nest, and fell asleep within 90 min. Dbh -/- mice failed to shred the lavender-scented nestlet, but still fell asleep. In contrast, controls sustained high levels of arousal throughout the predator odor test and did not build nests, while Dbh -/- mice were asleep by the 90-min time point, often in shredded bobcat urine-soaked nesting material. Compared with controls exposed to predator odor, Dbh -/- mice demonstrated decreased c-fos induction in the anterior cingulate cortex, lateral septum, periaqueductal gray, and bed nucleus of the stria terminalis, but increased c-fos in the locus coeruleus and medial amygdala. These data indicate that relative ratios of central NE and DA signaling coordinate the type and valence of responses to predator odor.

Genetic disruption of dopamine ß-hydroxylase dysregulates innate responses to predator odor in mice.

In rodents, exposure to predator odors such as cat urine acts as a severe stressor that engages innate defensive behaviors critical for survival in the wild. The neurotransmitters norepinephrine (NE) and dopamine (DA) modulate anxiety and predator odor responses, and we have shown previously that dopamine ß-hydroxylase knockout (Dbh -/-), which reduces NE and increases DA in mouse noradrenergic neurons, disrupts innate behaviors in response to mild stressors such as novelty. We examined the consequences of Dbh knockout (Dbh -/-) on responses to predator odor (bobcat urine) and compared them to Dbh-competent littermate controls. Over the first 10 min of predator odor exposure, controls exhibited robust defensive burying behavior, whereas Dbh -/- mice showed high levels of grooming. Defensive burying was potently suppressed in controls by drugs that reduce NE transmission, while excessive grooming in Dbh -/- mice was blocked by DA receptor antagonism. In response to a cotton square scented with a novel "neutral" odor (lavender), most control mice shredded the material, built a nest, and fell asleep within 90 min. Dbh -/- mice failed to shred the lavender-scented nestlet, but still fell asleep. In contrast, controls sustained high levels of arousal throughout the predator odor test and did not build nests, while Dbh -/- mice were asleep by the 90-min time point, often in shredded bobcat urine-soaked nesting material. Compared with controls exposed to predator odor, Dbh -/- mice demonstrated decreased c-fos induction in the anterior cingulate cortex, lateral septum, periaqueductal gray, and bed nucleus of the stria terminalis, but increased c-fos in the locus coeruleus and medial amygdala. These data indicate that relative ratios of central NE and DA signaling coordinate the type and valence of responses to predator odor.

Lateral septum DREADD activation alters male prairie vole prosocial and antisocial behaviors, not partner preferences.

Although much has been written on the topic of social behavior, many terms referring to different aspects of social behavior have become inappropriately conflated and the specific mechanisms governing them remains unclear. It is therefore critical that we disentangle the prosocial and antisocial elements associated with different forms of social behavior to fully understand the social brain. The lateral septum (LS) mediates social behaviors, emotional processes, and stress responses necessary for individuals to navigate day-to-day social interactions. The LS is particularly important in general and selective prosocial behavior (monogamy) but its role in how these two behavioral domains intersect is unclear. Here, we investigate the effects of chemogenetic-mediated LS activation on social responses in male prairie voles when they are 1) sex-naïve and generally affiliative and 2) after they become pair-bonded and display selective aggression. Amplifying neural activity in the LS augments same-sex social approach behaviors. Despite partner preference formation remaining unaltered, LS activation in pair-bonded males leads to reduced selective aggression while increasing social affiliative behaviors. These results suggest that LS activation alters behavior within certain social contexts, by increasing sex-naïve affiliative behaviors and reducing pair bonding-induced selective aggression with same-sex conspecifics, but not altering bonding with opposite-sex individuals.