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Mott, S. E.

Publications and source records attributed to Mott, S. E..

2 recordsLinked to original sources

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↗

Site-Specific Knockdown of Microglia in the Locus Coeruleus Regulates Hypervigilant Responses to Social Stress in Female Rats

BackgroundWomen are at increased risk for psychosocial stress-related anxiety disorders, yet mechanisms regulating this risk are unknown. Psychosocial stressors activate microglia, and the resulting neuroimmune responses that females exhibit heightened sensitivity to may serve as an etiological factor in their elevated risk. However, studies examining the role of microglia during stress in females are lacking. MethodsMicroglia were manipulated in the stress-sensitive locus coeruleus (LC) of female rats in the context of social stress in two ways. First, intra-LC lipopolysaccharide (LPS; 0 or 3g/side, n=5-6/group), a potent TLR4 agonist and microglial activator, was administered. One hour later, rats were exposed to control or an aggressive social defeat encounter between two males (WS, 15-min). In a separate study, females were treated with intra-LC or intra-central amygdala mannosylated liposomes containing clodronate (m-CLD; 0 or 25g/side, n=13-14/group), a compound toxic to microglia. WS-evoked burying, cardiovascular responses, and sucrose preference were measured. Brain and plasma cytokines were quantified, and cardiovascular telemetry assessed autonomic balance. ResultsIntra-LC LPS augmented the WS-induced burying response and increased plasma corticosterone and interleukin-1{beta} (IL-1{beta}). Further, the efficacy and selectivity of microinjected m-CLD was determined. In the context of WS, intra-LC m-CLD attenuated the hypervigilant burying response during WS as well as the accumulation of intra-LC IL-1{beta}. Intra-central amygdala m-CLD had no effect on witness stress-evoked behavior. ConclusionsThese studies highlight an innovative method for depleting microglia in a brain region specific manner and indicate that microglia in the LC differentially regulate hypervigilant WS-evoked behavioral and autonomic responses. HIGHLIGHTSO_LIIntra-LC LPS augments behavioral and physiological responses to social stress C_LIO_LIMannosylated liposomal clodronate site-specifically reduces microglial expression C_LIO_LIMicroglia within the locus coeruleus regulate stress-evoked behavior in female rats C_LI

neuroscience↗