Characterizing Sex Differences in Depressive-Like Behavior and Glial Brain Cell Changes Following Peripheral Nerve Injury in Mice.

Chronic pain and depression are intimately linked; the combination of the two leads to higher health care costs, lower quality of life, and worse treatment outcomes with both conditions exhibiting higher prevalence among women. In the current study, we examined the development of depressive-like behavior in male and female mice using the spared nerve injury (SNI) model of neuropathic pain. Males displayed increased immobility on the forced-swim test - a measure of depressive-like behavior - 2 weeks following injury, while females developed depressive-like behavior at 3-week. Since the pathogenesis of chronic pain and depression may involve overlapping mechanisms including the activation of microglial cells, we explored glial cell changes in brain regions associated with pain processing and affect. Immunohistochemical analyses revealed that microglial cells were more numerous in female SNI mice in the contralateral ventral anterior cingulate cortex (ACC), a brain region important for pain processing and affect behavior, 2-week following surgery. Microglial cell activation was not different between any of the groups for the dorsal ACC or nucleus accumbens. Analysis of astrocyte density did not reveal any significant changes in glial fibrillary acidic protein (GFAP) staining in the ACC or nucleus accumbens. Overall, the current study characterized peripheral nerve injury induced depression-like behavior in male and female mice, which may be associated with different patterns of glial cell activation in regions important for pain processing and affect.

Multiple dimensions of social motivation in adult female degus.

Many animals become more motivated to interact after a period of isolation. This phenomenon may involve general drives, e.g. for social touch or companionship, as well as drives that are specific to particular peers, and which ultimately serve to reestablish relationships between the individuals. Female degus are known to be affiliative with multiple other individuals, including unrelated and unfamiliar conspecifics, offering an opportunity to study social motivation independent from exclusive pair-bonds or overt, same-sex competition. We attempted to disentangle factors driving peer interaction by examining reunion behavior across several social isolation and separation manipulations. High levels of interaction were observed between adult females who had been separated even without isolation, revealing a drive to re-establish relationships with specific peers. The content of separation-only reunions differed from isolation, with the latter involving more early-session interaction, higher levels of allogrooming before rear-sniffing, and a higher ratio of chitter vocalizations. To assess whether post-isolation behavior was related to stress, we examined reunions following a non-social (footshock) stressor. Like isolation, footshock increased early-session interactions, but did not increase allogrooming before rear-sniffing or chittering, as compared with controls. To test whether separation-only reunion behavior shared qualities with relationship formation, we also examined reunions of new (stranger) dyads. Strangers exhibited higher levels of interaction than cagemates, with particularly high levels of late-session rear-sniffing. Like separation-only reunions, strangers showed more non-chitter vocalizations and lower levels of allogrooming before rear-sniffing. Across experiments, an exploratory clustering method was used to identify vocalizations that differed between conditions. This yielded promising leads for future investigation, including a chaff-type syllable that may have been more common during relationship renewal. Overall, results are consistent with the hypothesis that female degu reunions are supported by both general and peer-stimulus specific drives, expressed through the structure of physical and vocal interactions over time.

Prelimbic cortex glucocorticoid receptors regulate the stress-mediated inhibition of pain contagion in male mice.

Experiencing pain with a familiar individual can enhance one's own pain sensitivity, a process known as pain contagion. When experiencing pain with an unfamiliar individual, pain contagion is suppressed in males by activating the endocrine stress response. Here, we coupled a histological investigation with pharmacological and behavioral experiments to identify enhanced glucocorticoid receptor activity in the prelimbic subdivision of the medial prefrontal cortex as a candidate mechanism for suppressing pain contagion in stranger mice. Acute inhibition of glucocorticoid receptors in the prelimbic cortex was sufficient to elicit pain contagion in strangers, while their activation prevented pain contagion in cagemate dyads. Slice physiology recordings revealed enhanced excitatory transmission in stranger mice, an effect that was reversed by pre-treating mice with the corticosterone synthesis inhibitor metyrapone. Following removal from dyadic testing, stranger mice displayed enhanced affective-motivational pain behaviors when placed on an inescapable thermal stimulus, which were reversed by metyrapone. Together, our data suggest that the prelimbic cortex may play an integral role in modulating pain behavior within a social context and provide novel evidence towards the neural mechanism underlying the prevention of pain contagion.

The role of hedonics in the Human Affectome.

Experiencing pleasure and displeasure is a fundamental part of life. Hedonics guide behavior, affect decision-making, induce learning, and much more. As the positive and negative valence of feelings, hedonics are core processes that accompany emotion, motivation, and bodily states. Here, the affective neuroscience of pleasure and displeasure that has largely focused on the investigation of reward and pain processing, is reviewed. We describe the neurobiological systems of hedonics and factors that modulate hedonic experiences (e.g., cognition, learning, sensory input). Further, we review maladaptive and adaptive pleasure and displeasure functions in mental disorders and well-being, as well as the experience of aesthetics. As a centerpiece of the Human Affectome Project, language used to express pleasure and displeasure was also analyzed, and showed that most of these analyzed words overlap with expressions of emotions, actions, and bodily states. Our review shows that hedonics are typically investigated as processes that accompany other functions, but the mechanisms of hedonics (as core processes) have not been fully elucidated.

Observational fear learning in degus is correlated with temporal vocalization patterns.

Some animals learn to fear a situation after observing another individual come to harm, and this learning is influenced by the animals' social relationship and history. An important but sometimes overlooked factor in studies of observational fear learning is that social context not only affects observers, but may also influence the behavior and communications expressed by those being observed. Here we sought to investigate whether observational fear learning in the degu (Octodon degus) is affected by social familiarity, and the degree to which vocal expressions of alarm or distress contribute. 'Demonstrator' degus underwent contextual fear conditioning in the presence of a cagemate or stranger observer. Among the 15 male pairs, observers of familiar demonstrators exhibited higher freezing rates than observers of strangers when returned to the conditioning environment one day later. Observer freezing during testing was, however, also related to the proportion of short- versus long- inter-call-intervals (ICIs) in vocalizations recorded during prior conditioning. In a regression model that included both social relationship and ICI patterns, only the latter was significant. Further investigation of vocalizations, including use of a novel, directed k-means clustering approach, suggested that temporal structure rather than tonal variations may have been responsible for communicating danger. These data offer insight into how different expressions of distress or fear may impact an observer, adding to the complexity of social context effects in studies of empathy and social cognition. The experiments also offer new data on degu alarm calls and a potentially novel methodological approach to complex vocalizations.