Effects of Stress and Ethanol on the Locus Coeruleus to Medial Prefrontal Cortex Circuit in Male and Female Mice

Authors: Misha Muneeb, Gisele Fumarola, Natalia Orozco, Marcis Scroger, Florence Varodayan

Field of Study: Integrative Neuroscience

Program Affiliation: Summer Scholars and Artists Program (SSAP)

Faculty Mentors: Florence Varodayan

Easel: 8

Timeslot: Afternoon

Abstract: The locus coeruleus (LC) modulates stress by releasing norepinephrine (NE) to brain regions such as the medial prefrontal cortex (mPFC). LC dysregulation has been implicated in alcohol use disorder (AUD) and stress-related disorders. Under stressful conditions, the LC releases excessive NE, which impairs mPFC functioning. However, the LC-mPFC circuit is not well defined, especially in the context of disease states and across sexes. Therefore, the basal LC-mPFC circuit was examined in male and female mice using a retrograde fluorescent tracer in the mPFC and immunofluorescence. Additionally, LC activation induced by acute stress and ethanol exposure was characterized. Using immunofluorescence, tyrosine hydroxylase was used to identify LC NE neurons and the immediate early c-Fos gene was used to assess activation. These findings may uncover sex differences in stress- and alcohol-induced LC activation and the basal LC-mPFC circuit, shedding light on the vulnerability to and comorbidity of anxiety disorders and AUD.