Dorsal CA1 lesions of the hippocampus impact mating tactics in prairie voles by shifting non-monogamous males' use of space to resemble monogamous males.

Alternative mating tactics within mating systems are characterized by discrete patterns of spatio-temporal overlap with same-and opposite-sex conspecifics and mating-relevant outcomes. Socially monogamous "residents" maintain relatively small home range sizes, have territories that almost exclusively overlap with their mating partners, and are more likely to produce offspring than non-bonded "wandering" conspecifics. Because mating tactics appear to be so closely tied to patterns of space use, differences in spatial cognitive abilities might differentially impact individual males' decisions to adopt a particular mating tactic and/or how efficient they are within their chosen mating tactic. Yet few studies have considered how the hippocampus, a brain region important for encoding cognitive maps and for processing contextual information, might impact how individuals adopt mating tactics or the spatio-temporal behaviors closely associated with them. We assessed the impact of lesions to the dorsal CA1 (dCA1) region of the hippocampus on male prairie vole space use, reproductive success, and mating tactics in semi-natural outdoor field conditions. Interestingly, dCA1 lesions did not impact the proportion of males that adopted resident or wandering mating tactics, and dCA1 lesions did not impact a male's ability to form a pair bond in the lab. In contrast, we found that lesioning the dCA1 shifted the home range size of reproductively successful and unsuccessful males. Furthermore, we found that patterns of space use among residents were unaffected by dCA1 lesions, whereas wanderers with dCA1 lesions showed pronounced reductions of their space use habits and resembled non-lesioned residents. Collectively, our study supports the hypothesis that wanderer male prairie voles rely on dCA1-mediated spatial cognition to navigate their world in a way that resident males do not. Such differences might have implications for how individuals efficiently attract and defend mates, obtain resources, defend territories, and outcompete rivals.

Motherhood and DREADD manipulation of the nucleus accumbens weaken established pair bonds in female prairie voles.

Monogamous pair bonding has evolved to enhance reproductive success and ensure offspring survival. Although the behavioral and neural mechanisms regulating the formation of pair bonds have been relatively well outlined, how these relationships are regulated and maintained across the lifetime of an individual remains relatively unexplored. One way to explore this is to study the maintenance of a social bond across a major life-history transition. The transition to motherhood is among the most poignant moments in the life history of a female, and is associated with significant neural and behavioral changes and shifting priorities. The nucleus accumbens (NAc) is known to modulate social valence and is central to mammalian pair bonding. In this study, we investigated two mechanisms driving variation in bond strength in the socially monogamous prairie vole (Microtus ochrogaster). We manipulated neural activity of the NAc at two distinct stages of life-history, before and after the birth of offspring, to assess how neural activity and social contexts modulate female pair bond strength. Our results showed DREADD (Designer Receptor Exclusively Activated by Designer Drugs) inhibition of the NAc decreases affiliative behavior towards the mating partner, whereas DREADD activation of the NAc increases affiliative behavior of strangers, thereby decreasing social selectivity. We also found a robust "birth effect" on pair bond strength, such that bonds with partners were weakened after the birth of offspring, an effect not attributable to the amount of cohabitation time with a partner. Overall, our data support the hypotheses that NAc activity modulates reward/saliency within the social brain in different ways, and that motherhood comes with a cost for the bond strength between mating partners.

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.

Synergistic consequences of early-life social isolation and chronic stress impact coping and neural mechanisms underlying male prairie vole susceptibility and resilience.

Chronic stress can be challenging, lead to maladaptive coping strategies, and cause negative mental and physical health outcomes. Early-life adversity exposes developing young to physical or psychological experiences that risks surpassing their capacity to effectively cope, thereby impacting their lifetime physical and mental wellbeing. Sensitivity to stressful events, like social isolation, has the potential to magnify stress-coping. Chronic stress through social defeat is an established paradigm that models adverse early-life experiences and can trigger enduring alterations in behavioral and neural phenotypes. To assess the degree to which stress resilience and sensitivity stemming from early-life chronic stress impact sociability, we exposed male prairie voles to chronic social defeat stress (CSDS) during adolescence. We simultaneously exposed subjects to either social isolation (CSDS+Isol) or group housing (CSDS+Soc) during this crucial time of development. On PND41, all subjects underwent a social approach test to examine the immediate impact of isolation, CSDS, or their combined effects on sociability. Unlike the CSDS+Isol group which primarily displayed social avoidance, the CSDS+Soc group was split by individuals exhibiting susceptible or resilient stress phenotypes. Notably, the Control+Soc and CSDS+Soc animals and their cage-mates significantly gained body weight between PND31 and PND40, whereas the Control+Isol and CSDS+Isol animals did not. These results suggest that the effects of early-life stress may be mitigated by having access to social support. Vasopressin, oxytocin, and opioids and their receptors (avpr1a, oxtr, oprk1, oprm1, and oprd1) are known to modulate social and stress-coping behaviors in the lateral septum (LS). Therefore, we did an mRNA expression analysis with RT-qPCR of the avpr1a, oxtr, oprk1, oprm1, and oprd1 genes to show that isolation and CSDS, or their collective influence, can potentially differentially bias sensitivity of the LS to early-life stressors. Collectively, our study supports the impact and dimensionality of early-life adversity because the type (isolation vs. CSDS), duration (acute vs. chronic), and combination (isolation + CSDS) of stressors can dynamically alter behavioral and neural outcomes.

Optogenetic inhibition of medial prefrontal cortex projections to the nucleus accumbens core and methyl supplementation via L-Methionine attenuates cocaine-primed reinstatement.

DNA methylation has been identified as a powerful and activity-dependent regulator of changes in the brain that may underlie neuroadaptations in response to various types of stimuli, including exposure to drugs of abuse. Indeed, the medial prefrontal cortex (mPFC) projections to the nucleus accumbens (NAc) are critically important for reinstated cocaine-seeking in a rodent model of cocaine relapse. This circuitry undergoes several epigenetic modifications following cocaine exposure, including changes in DNA methylation that are associated with drug-seeking behavior. We have previously shown that methyl supplementation via L-Methionine (MET) administration attenuates cocaine-seeking behavior and reverses expression and methylation patterns of the immediate early gene c-fos, suggesting that MET may act by altering the excitability of this circuitry during cocaine reinstatement. In the current study, male rats were microinjected with an adeno-associated virus overexpressing halorhodopsin in the mPFC, optical fibers were surgically implanted into the NAc, and the rats were given injections of MET daily. Rats underwent acquisition of cocaine self-administration (0.75 mg/kg/infusion, 2-h sessions) followed by extinction training in the absence of drug-paired cues. Two reinstatement tests were conducted: cue-induced reinstatement without optogenetic manipulations and cocaine-primed reinstatement with optogenetic inhibition of mPFC-to-NAc projections. There were no group differences before the cocaine-primed reinstatement session, and all groups showed robust cue-induced reinstatement. Both rats treated with MET and rats that received mPFC-to-NAc inhibition showed an abolishment of cocaine-primed reinstatement, suggesting that systemic methyl supplementation may act through this critical circuity.