Project 1: The Reciprocal Relationship between Binge Drinking and Astrocytic Signaling

Project Abstract: Excessive binge alcohol consumption causes major health and socio-economic issues within
the United States. Unfortunately, minorities in this country are disproportionately burdened by these problems
despite equal incidences of binge drinking. Finding ways to reduce binge like consumption therefore remains an
important field of research to combat health disparities and decrease the development of ethanol dependence.
This project seeks to determine if astrocytes and the neuroimmune system represent novel targets by which to
curb excessive consumption. This grant determines the influence of excessive ethanol on astrocytic activation
and function in the hippocampus as well if the proinflammatory cytokines are responsible for glial maladaptations
(Aim 1). Because sex-differences can alter neuroimmune responses, these studies will elucidate the impact of
sex on both astrocyte activation and their function. Secondly, these studies will determine if hippocampal
astrocytic signaling can be switched to reverse the influences of ethanol on the increased proinflammatory
microenvironment and decreased glutamatergic tone of the hippocampus (Aim 2). Finally, because both
glutamate and proinflammatory cytokines can impact hippocampal dependent memory tasks and consummatory
behaviors, these experiments will determine the impact of astrocytic signaling on ethanol consumption and
alcohol-induced cognitive deficits (Aim 2). The development of astrocyte specific DREADDs allows us to
manipulate G-protein coupled receptor signaling in the hippocampus using site directed stereotactic viral
delivery. Altogether, these two aims will test our overall hypothesis that there is a reciprocal and reinforcing
relationship between alcohol and astrocyte activation mediated by the influence of astrocytes on glutamatergic
tone and proinflammatory signaling cascades. These innovative studies will provide insight into the role of
astrocytes in the transition to alcohol dependence as well as the influence of alcohol-induced neuroimmune
dysregulation on the astrocytic response.