A test of the social behavior network reveals differential patterns of neural responses to social novelty in bonded, but not non-bonded, male prairie voles.

The social behavior network (SBN) has provided a framework for understanding the neural control of social behavior. The original SBN hypothesis proposed this network modulates social behavior and should exhibit distinct patterns of neural activity across nodes, which correspond to distinct social contexts. Despite its tremendous impact on the field of social neuroscience, no study has directly tested this hypothesis. Thus, we assessed Fos responses across the SBN of male prairie voles (Microtus ochrogaster). Virgin/non-bonded and pair bonded subjects were exposed to a sibling cagemate or pair bonded partner, novel female, novel male, novel meadow vole, novel object, or no stimulus. Inconsistent with the original SBN hypothesis, we did not find profoundly different patterns of neural responses across the SBN for different contexts, but instead found that the SBN generated significantly different patterns of activity in response to social novelty in pair bonded, but not non-bonded males. These findings suggest that non-bonded male prairie voles may perceive social novelty differently from pair bonded males or that SBN functionality undergoes substantial changes after pair bonding. This study reveals novel information about bond-dependent, context-specific neural responsivity in male prairie voles and suggests that the SBN may be particularly important for processing social salience. Further, our study suggests there is a need to reconceptualize the framework of how the SBN modulates social behavior.

Behavioral, neurochemical, and neuroimmune changes associated with social buffering and stress contagion.

Social buffering can provide protective effects on stress responses and their subsequent negative health outcomes. Although social buffering is beneficial for the recipient, it can also have anxiogenic effects on the provider of the social buffering - a phenomena referred to as stress contagion. Social buffering and stress contagion usually occur together, but they have traditionally been studied independently, thus limiting our understanding of this dyadic social interaction. In the present study, we examined the effects of preventative social buffering and stress contagion in socially monogamous prairie voles (Microtus ochrogaster). We tested the hypothesis that this dynamic social interaction is associated with coordinated alterations in behaviors, neurochemical activation, and neuroimmune responses. To do so, adult male prairie voles were stressed via an acute immobilization restraint tube (IMO) either alone (Alone) or with their previously pair-bonded female partner (Partner) in the cage for 1 h. In contrast, females were placed in a cage containing either an empty IMO tube (Empty) or one that contained their pair-bonded male (Partner). Anxiety-like behavior was tested on the elevated plus maze (EPM) following the 60-mins test and brain sections were processed for neurochemical/neuroimmune marker labeling for all subjects. Our data indicate that females in the Partner group were in contact with and sniffed the IMO tube more, showed fewer anxiety-like behaviors, and had a higher level of oxytocin expression in the paraventricular nucleus of the hypothalamus (PVN) compared to the Empty group females. Males in the Partner group had lower levels of anxiety-like behavior during the EPM test, greater activation of corticotropin-releasing hormone expressing neurons in the PVN, lower activation of serotonin neurons in the dorsal raphe, and lower levels of microgliosis in the nucleus accumbens. Taken together, these data suggest brain region- and neurochemical-specific alterations as well as neuroinflammatory changes that may be involved in the regulation of social buffering and stress contagion behaviors.

Post-weaning Social Isolation in Male and Female Prairie Voles: Impacts on Central and Peripheral Immune System.

The socially monogamous prairie vole (Microtus ochrogaster) offers a unique opportunity to examine the impacts of adolescent social isolation on the brain, immune system, and behavior. In the current study, male and female prairie voles were randomly assigned to be housed alone or with a same-sex cagemate after weaning (i.e., on postnatal day 21-22) for a 6-week period. Thereafter, subjects were tested for anxiety-like and depressive-like behaviors using the elevated plus maze (EPM) and Forced Swim Test (FST), respectively. Blood was collected to measure peripheral cytokine levels, and brain tissue was processed for microglial density in various brain regions, including the Nucleus Accumbens (NAcc), Medial Amygdala (MeA), Central Amygdala (CeA), Bed Nucleus of the Stria Terminalis (BNST), and Paraventricular Nucleus of the Hypothalamus (PVN). Sex differences were found in EPM and FST behaviors, where male voles had significantly lower total arm entries in the EPM as well as lower latency to immobility in the FST compared to females. A sex by treatment effect was found in peripheral IL-1ß levels, where isolated males had a lower level of IL-1ß compared to cohoused females. Post-weaning social isolation also altered microglial density in a brain region-specific manner. Isolated voles had higher microglial density in the NAcc, MeA, and CeA, but lower microglial density in the dorsal BNST. Cohoused male voles also had higher microglial density in the PVN compared to cohoused females. Taken together, these data suggest that post-weaning social housing environments can alter peripheral and central immune systems in prairie voles, highlighting a potential role for the immune system in shaping isolation-induced alterations to the brain and behavior.

Dissociating the effects of dopamine D2 receptors on effort-based versus value-based decision making using a novel behavioral approach.

Cost-benefit decision making is essential for organisms to adapt to their ever-changing environment. Most studies of cost-benefit decision making involve choice conditions in which effort and value are varied simultaneously. This prevents identification of the aspects of cost-benefit decision making that are affected by experimental manipulations. We developed operant assays to isolate the individual impacts of effort and value manipulations on cost-benefit decision making. In the concurrent effort choice (CEC) task, mice choose between exerting two distinct types of effort: the number of responses and the duration of a response, to earn the same reward. By parametrically varying response cost, psychometric functions are obtained that reflect how the two types of effort scale against one another. Direct manipulations of effort shift the functions. Because reward value is held constant in this task, differences in scaling of the two response types must be related to the effort manipulations. In the concurrent value choice (CVC) task, mice make the same type of response to earn rewards of different value (e.g., pellets vs. sucrose solutions). Here the effort required to earn one reward type is parametrically varied to obtain the psychometric function that scales the value of the two rewards into the number of responses subjects will pay to earn one reward over the other. Direct value manipulations shift these functions. We tested the effect of the dopamine D2 receptor antagonist, haloperidol, on performance in the CEC and CVC assays and found that D2R signaling is important for effort-based, but not value-based decision making. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Time-scale-invariant information-theoretic contingencies in discrimination learning.

Animals optimize their behavior to maximize rewards by utilizing cues from the environment. In discrimination learning, cues signal when rewards can and cannot be earned by making a particular response. In our experiment, we trained male mice to press a lever to receive a reward on a random interval schedule. We then introduced a prolonged tone (20, 40, or 80 sec), during which no rewards could be earned. We sought to test our hypothesis that the duration of the tone and frequency of reward during the inter-tone-intervals affect the informativeness of cues and led to differences in discriminative behavior. Learning was expressed as an increase in lever pressing during the intertrial interval (ITI) and, when the informativeness of the cue was high, animals also reduced their lever pressing during the tone. Additionally, we found that the depth of discriminative learning was linearly related to the informativeness of the cues. Our results show that the time-scale invariant information-theoretic definition of contingency applied to excitatory conditioning can also be applied to inhibitory conditioning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

An Interaction between Serotonin Receptor Signaling and Dopamine Enhances Goal-Directed Vigor and Persistence in Mice.

The functionally selective 5-HT2C receptor ligand SB242084 can increase motivation and have rapid onset anti-depressant-like effects. We sought to identify the specific behavioral effects of SB242084 treatment and elucidate the mechanism in female and male mice. Using a quantitative behavioral approach, we determined that SB242084 increases the vigor and persistence of goal-directed activity across different types of physical work, particularly when work requirements are demanding. We found this influence of SB242084 on effort, rather than reward to be reflected in striatal DA measured during behavior. Using in vivo fast scan cyclic voltammetry, we found that SB242084 has no effect on reward-related phasic DA release in the NAc. Using in vivo microdialysis to measure tonic changes in extracellular DA, we also found no changes in the NAc. In contrast, SB242084 treatment increases extracellular DA in the dorsomedial striatum, an area that plays a key role in response vigor. These findings have several implications. At the behavioral level, this work shows that the capacity to work in demanding situations can be increased, without a generalized increase in motor activity or reward value. At the circuit level, we identified a pathway restricted potentiation of DA release and showed that this was the reason for the increased response vigor. At the cellular level, we show that a specific serotonin receptor cross talks to the DA system. Together, this information provides promise for the development of treatments for apathy, a serious clinical condition that can afflict patients with psychiatric and neurological disorders.SIGNIFICANCE STATEMENT Motivated behaviors are modulated by reward value, effort demands, and cost-benefit computations. This information drives the decision to act, which action to select, and the intensity with which the selected action is performed. Because these behavioral processes are all regulated by DA signaling, it is very difficult to influence selected aspects of motivated behavior without affecting others. Here we identify a pharmacological treatment that increases the vigor and persistence of responding in mice, without increasing generalized activity or changing reactions to rewards. We show that the 5-HT2C-selective ligand boosts motivation by potentiating activity-dependent DA release in the dorsomedial striatum. These results reveal a novel strategy for treating patients with motivational deficits, avolition, or apathy.