Biology subjects

Edgar, E. L.

Publications and source records attributed to Edgar, E. L..

3 recordsLinked to original sources

bioRxiv2023

Impaired microglia-mediated synaptic pruning in the nucleus accumbens during adolescence results in persistent dysregulation of familiar, but not novel social interactions in sex-specific ways

Evolutionarily conserved, peer-directed social behaviors are essential to participate in many aspects of human society. These behaviors directly impact psychological, physiological, and behavioral maturation. Adolescence is an evolutionarily conserved period during which reward-related behaviors, including social behaviors, develop via developmental plasticity in the mesolimbic dopaminergic reward circuitry of the brain. The nucleus accumbens (NAc) is an intermediate reward relay center that develops during adolescence and mediates both social behaviors and dopaminergic signaling. In several developing brain regions, synaptic pruning mediated by microglia, the resident immune cells of the brain, is important for normal behavioral development. In rats, we previously demonstrated that microglial synaptic pruning also mediates NAc and social development during sex-specific adolescent periods and via sex-specific synaptic pruning targets. In this report, we demonstrate that interrupting microglial pruning in NAc during adolescence persistently dysregulates social behavior towards a familiar, but not novel social partner in both sexes, via sex-specific behavioral expression. This leads us to infer that naturally occurring NAc pruning serves to reduce social behaviors primarily directed toward a familiar conspecific in both sexes, but in sex-specific ways.

neuroscience↗

bioRxiv2023

Social aging trajectories are sex-specific, sensitive to adolescent stress, and most robustly revealed during social tests with familiar stimuli

Social networks and support are integral to health and wellness across the lifespan, and social engagement may be particularly important during aging. However, social behavior and social cognition decline naturally during aging across species. Social behaviors are in part supported by the reward circuitry, a network of brain regions that develops during adolescence. We published that male and female rats undergo adolescent social development during sex-specific periods, pre-early adolescence in females and early-mid adolescence males. Although males and females have highly dimorphic development, expression, and valuation of social behaviors, there is relatively little data indicating whether social aging is the same or different between the sexes. Thus, we sought to test two hypotheses: (1) natural social aging will be sex-speciifc, and (2) social isolation stress restricted to sex-specific adolescent critical periods for social development would impact social aging in sex-specific ways. To do this, we bred male and female rats in-house, and divided them randomly to receive either social isolation for one week during each sexs respective critical period, or no manipulation. We followed their social aging trajectory with a battery of five tests at 3, 7, and 11 months of age. We observed clear social aging signatures in all tests administered, but sex differences in natural social aging were most robustly observed when a familiar social stimulus was included in the test. We also observed that adolescent isolation did impact social behavior, in both age-independent and age-dependent ways, that were entirely sex-specific. Please note, this preprint will not be pushed further to publication (by me, AMK), as I am leaving academia. So, its going to be written more conversationally.

neuroscience↗

bioRxiv2023

Morphine exposure during adolescence induces enduring social changes dependent on adolescent stage of exposure, sex, and social test

Drug exposure during adolescence, when the reward circuitry of the brain is developing, can permanently impact reward-related behavior. Epidemiological studies show that opioid treatment during adolescence, such as pain management for a dental procedure or surgery, increases the incidence of psychiatric illness including substance use disorders. Moreover, the opioid epidemic currently in the United States is affecting younger individuals raising the impetus to understand the pathogenesis of the negative effects of opioids. One reward-related behavior that develops during adolescence is social behavior. We previously demonstrated that social development occurs in rats during sex-specific adolescent periods: early to mid-adolescence in males (postnatal day (P)30-40) and pre-early adolescence in females (P20-30). We thus hypothesized that morphine exposure during the female critical period would result in adult sociability deficits in females, but not males, and morphine administered during the male critical period would result in adult sociability deficits in males, but not females. We found that morphine exposure during the female critical period primarily resulted in deficits in sociability in females, while morphine exposure during the male critical period primarily resulted in deficits in sociability primarily in males. However, depending on the test performed and the social parameter measured, social alterations could be found in both sexes that received morphine exposure at either adolescent stage. These data indicate that when drug exposure occurs during adolescence, and how the endpoint data are measured, will play a large role in determining the effects of drug exposures on social development.

neuroscience↗