Defense Date
2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Neuroscience
First Advisor
Jennifer Wolstenholme
Abstract
Adolescence is characterized by heightened social interaction and risk-taking behavior. Disruptions to cortical development by binge ethanol or social isolation can lead to attention, social, and cognitive deficits later in life, and increase risk for alcohol use disorders. During adolescence, proper development of a monosynaptic connection from the ventral hippocampus (vHip) to the medial prefrontal cortex (mPFC) is critical to proper social and working memory. We ask whether these factors affect neurobiological factors such as gene expression and the role of the vHipmPFC circuit in these behaviors. Social stress was modeled by social isolation (aSI) during adolescence. We expect aSI mice will drink more than group housed and have altered social and cognitive behaviors. We expect excitation of vHipmPFC neurons will improve performance on a three-chamber social preference task in aSI mice and reduce drinking in adulthood. We found differential gene expression due to housing and ethanol related to synaptic plasticity and methylation and impaired Barnes maze probe trial performance after aSI. In adolescence and adulthood, aSI mice drank more than group housed in a modified DID paradigm. aSI+/- DID mice were injected with a rAAV-Cre-GFP virus in the mPFC and a Cre-dependent inhibitory, excitatory, or control DREADD in the vHip. 20 minutes prior to testing, mice were injected with 3.2mg/kg of the DREADD ligand Deschloroclozapine i.p. Activation of vHipmPFC neurons decreased ethanol intake in aSI+DID mice and Gi mediated inhibition reduced drinking in aSI-DID compared to mCherry controls. There were no changes in the three-chamber social preference test performance.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
8-6-2024