Automated tracking of locomotor sensitization to alcohol in mice

Live Poster Session: Zoom Link
Thursday, July 30th 1:15-2:30pm EDT

Tess Brunner
Tess Brunner

Tess Brunner is a rising senior (‘21) from Sudbury, Massachusetts, where she attended Lincoln-Sudbury Regional High School. She is majoring in Neuroscience & Behavior with a Certificate in Informatics & Modeling in the Integrative Genomic Sciences pathway. She’s a member of the women’s ultimate frisbee team Vicious Circles and is part of the Wesleyan Doula Project to promote reproductive justice. In addition, Tess lived in Farm House last year and has worked on Long Lane Farm, and is interested in hiking and science fiction. She plans to attend an MD/PhD program to continue her career in medical research.

Abstract: Alcohol use disorders are a leading health problem globally, and understanding the neuroadaptations caused by this drug is critical to providing treatment, honing prevention strategies, and increasing public education. Sensitization to chronic alcohol reflects changes in mesocorticolimbic dopamine signaling that is integral to both reward and locomotion. These neuroadaptations have repeatedly been demonstrated following chronic use of psychostimulants that directly engage this dopamine pathway. Rodent models and human studies have shown that consistent alcohol consumption also leads to sensitization to the locomotor effects of alcohol, reflecting alcohol’s effects on dopamine signaling and the mesolimbic reward pathway. Individual differences in the degree of locomotor sensitization may reflect variability in the development of alcohol-induced molecular adaptations. Mice that develop locomotor sensitization have been shown to have greater preference for alcohol. As our lab has previously shown a relationship between escalating alcohol intake and GABAA receptor expression, we wished to determine whether locomotor sensitization was similarly associated with changes in GABAA receptors. These inhibitory GABAA receptors may be expressed by dopamine neurons in the mesocorticolimbic system and GABAergic interneurons that synapse on these dopamine cells. Thus, we hypothesize that individual differences in locomotor sensitization would reflect cell-type specific changes in GABAA expression. Alcohol, however, also affects stress systems, and these effects may intersect. In this study, we analyzed the relationship between locomotion as a sensitization marker and the neuronal mesocorticolimbic changes reflective of stress-induced changes in dopamine signaling. For these analyses, we compared mouse locomotor patterns before and after consistent alcohol administration to detect individual differences in the development of locomotor sensitization, quantified blood corticosterone levels as a stress response marker, and used the neuronal activity marker c-Fos to measure stress-induced changes in cell activity. After comparing numerous object tracking programs based on efficiency, accuracy of tracking data and versatility of function, we chose the ImageJ plugin AnimalTracker to obtain the most reliable quantification of locomotor activity in archived videos. Using these analyses, we will examine correlations between the behavioral symptoms and the neurological changes from alcohol use. In addition, this lab has found sex differences in protracted alcohol withdrawal symptoms and we will determine whether the investigated sensitization neuroadaptations also demonstrate sex differences. By connecting both the dopaminergic signaling and changes in stress reactivity to a mouse model of alcohol sensitization, we can increase understanding of the common mechanisms that may underlie alcohol’s effects on reward and stress. These results will help us towards predicting relapse likelihood based on sensitization behaviors, as well as possible cellular targets for counteracting the negative effects of alcohol use on stress.

Poster_TB_July_27_2020-Tess-Brunner

Live Poster Session: Zoom Link
Thursday, July 30th 1:15-2:30pm EDT

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