Mariam Zayour | 2025 I.S. Symposium

Name: Mariam Zayour
Title: Ethanol-induced conditioned-place preference reveals alcohol-seeking engram neurons in the ventral tegmental area and centrally-projecting Edinger-Westphal nucleus.
Major: Neurobiology
Minor:Chemistry
Advisors: Dr. Alfredo Zuniga; Dr. Seth Kelly

Alcohol use disorder is a chronic disease characterized by compulsive alcohol intake, negative emotional states during periods of abstinence, and repeated relapse events. Long-term changes within the brain caused by alcohol misuse, can leave individuals vulnerable to relapse. Associative learning plays an important role in relapse, where an association of a specific stimulus or cue is paired with the intoxicating effects of alcohol. Repeated pairings of stimuli and alcohol cause the two to be linked. Over time, exposure to stimuli associated with alcohol can elicit responses that may promote relapse. The conditioned place preference (CPP) model has been used to assess the reinforcing effects of drugs, including alcohol. Neurons involved in associative learning are more likely to reactivate upon exposure to environmental stimuli associated with alcohol. To better understand how alcohol-context associations are stored within the brain, we used ethanol-induced CPP in a TRAP2 transgenic mouse system, which allowed for tamoxifen-induced permanent genetic labeling of neurons via expression of a green fluorescent protein (ZsGreen). Thus, allowing us to identify and visualize neurons active during alcohol-seeking after CPP. Using a biased approach in which ethanol was paired with an unfavored context failed to produce ethanol-induced CPP. However, an unbiased approach was sufficient to induce ethanol CPP in TRAP2 mice. When analyzing the expression patterns of ZsGreen, robust expression was found in the ventral tegmental area (VTA) and centrally-projecting Edinger-Westphal Nucleus (EWcp). These regions have been linked to alcohol consumption and reward-mediated behaviors. Surprisingly, Immunohistochemistry analysis indicated that only a minority of these engram neurons in the VTA were dopaminergic. Future work trying to characterize the properties of these engrams in the VTA and EWcp will be important to understanding their role in driving alcohol-seeking behaviors.

Posted in Symposium 2025 on May 1, 2025.