Biology subjects

Magee, S. N.

Publications and source records attributed to Magee, S. N..

3 recordsLinked to original sources

bioRxiv2025

A water-based platform test of paired or group social dominance and neural activity in male and female mice

Social hierarchy is an evolutionarily-conserved phenomenon determined by social dominance behavior that has profound influence on health and relevance in neuropsychiatric disorders. Despite this, the neural mechanisms underlying social dominance remain unclear and current behavioral tests are limited. Here, we describe a novel platform test of social dominance where mice compete for space on a small, elevated platform surrounded by cold water and rank is calculated by total time spent on platform. To validate this assay, we conducted tube test followed by platform test in cages of male and female mice. We observed stable rank in both sexes using the platform test and saw notable differences in overall cage hierarchy between tube and platform. Motivated behavior as measured by attempts to get on the platform was reduced over time. Cooperative behavior as measured by shared time on platform was observed across all ranks but predominantly demonstrated by subordinate mice. Corticosterone levels were significantly higher in females but showed no rank-specific differences. Neuronal activity in the prefrontal cortex was not rank-dependent, however activity in the habenula scaled with rank in both sexes and was significantly correlated with dominance in males. We also investigated group social dynamics using the platform test and identified stable hierarchies with more exaggerated dominance compared to paired platform testing. These results introduce the platform test as a novel method for assessing social dominance behavior in male and female mice, which can be used to further our understanding of the neurobiology underlying social hierarchy.

neuroscience↗

bioRxiv2024

The persistent effects of predator odor stressor enhance interoceptive sensitivity to alcohol through GABA-A receptor adaptations in the prelimbic cortex in male, but not female rats

BackgroundTraumatic stress is associated with high rates of problematic alcohol use, but how the persistent effects of trauma impact sensitivity to alcohol remain unknown. This study examined the persistent effects of traumatic stress exposure on sensitivity to alcohol and underlying neurobiological mechanisms in rats. MethodsMale (N=98) and female (N=98) Long-Evans rats were exposed to the predator odor TMT, and two weeks later, molecular, neuronal, and behavioral sensitivity to alcohol were assessed. Next, rats were trained to discriminate alcohol from water (male N=70; female N=56), and the impact of TMT on interoceptive sensitivity to alcohol and the alcohol-like effects of systemic GABAA receptor activation were evaluated. Lastly, functional involvement of GABAA and NMDA receptors in the prelimbic cortex (PrL) and the anterior insular cortex (aIC) was investigated. ResultsTMT exposure sex-dependently altered PrL Gabra1, and elevated aIC Grin2b and Grin2c in males. TMT increased PrL c-Fos in males, which was attenuated by alcohol administration. Alcohol-induced locomotor and startle response effects were attenuated in the TMT group in both sexes. TMT exposure potentiated interoceptive sensitivity to alcohol in males but not in females, and this effect was driven by GABAA receptors in the PrL. Greater stress reactivity during TMT exposure was associated with higher interoceptive sensitivity to alcohol, and alcohol exposure history was linked to a heightened stress response to TMT in males. ConclusionsTraumatic stress increased interoceptive sensitivity to alcohol in males, but not females, through PrL GABAA receptor adaptations, potentially enhancing the stimulatory, and by extension the rewarding, effects of alcohol.

neuroscience↗

bioRxiv2020

Forced Abstinence from Alcohol Induces Sex-Specific Depression-like Behavioral and Neural Adaptations in Somatostatin Neurons in Cortical and Amygdalar Regions

Forced abstinence (FA) from alcohol has been shown to produce a variety of anxiety- and depression- like symptoms in animal models. Somatostatin (SST) neurons, a subtype of GABAergic neurons found throughout the brain, are a novel neural target with potential treatment implications in affective disorders, yet their role in alcohol use disorders (AUD) remains to be explored. Here, we examined the neuroadaptations of SST neurons during forced abstinence from voluntary alcohol consumption. Following six weeks of two-bottle choice alcohol consumption and protracted forced abstinence, male and female C57BL/6J mice exhibited a heightened, but sex-specific, depressive-like behavioral profile in the sucrose preference test (SPT) and forced swim test (FST), without changes in anxiety-like behaviors in the elevated plus maze (EPM) and open field test (OFT). FST-induced cFos expressions in the prefrontal cortex (PFC) and ventral bed nucleus of the stria terminalis (vBNST) were altered in FA-exposed female mice only, suggesting a sex-specific effect of forced abstinence on the neural response to acute stress. SST immunoreactivity in these regions was unaffected by forced abstinence, while differences were seen in SST/cFos co-expression in the vBNST. No differences in cFos or SST immunoreactivity were seen in the lateral central nucleus of the amygdala (CEA) and the basolateral amygdala (BLA). Additionally, SST neurons displayed opposing alterations in the PFC and vBNST, with heightened intrinsic excitability in the PFC and diminished intrinsic excitability in the vBNST. These findings provide an overall framework of forced abstinence-induced neuroadaptations in these key brain regions involved in emotional regulation and processing.

neuroscience↗