Eve Glenn is on a mission to better understand addiction and to help create more effective treatments for alcohol and substance use disorders.
Glenn, a senior at Brown University, split her time growing up between Germany and Florida, and witnessed a number of friends fall into substance use dependencies. Glenn said she became accustomed to the sight of her peers walking to the village park in Stuttgart with a cigarette hanging from their lips and bottles of alcohol in their hands.
“The melting pot of culture and migration made it so that many of my closest friends were refugees seeking asylum from war-torn homes against mounting socioeconomic tension,” Glenn said. “I heard my friends’ stories and witnessed their challenges with drugs. This led me to realize how something as debilitating as addiction could so easily take hold.”
As she moved from Germany to the U.S., she said it felt as though the shadow of addiction followed her.
“The people, culture, reasons and substances of choice were always different, but the crippling effects of this disorder remained the same,” Glenn said. “My empathy for these individuals inspired an exploration of this widespread and personalized disorder.”
Glenn’s global background inspired her to pursue a neuroscience degree at Brown with a focus on neurobiological mechanisms of addiction and disease. Using the fruit fly as a model organism, Glenn is conducting independent research on self-administration and alcohol use disorders in the laboratory of Karla Kaun, an associate professor of neuroscience who is affiliated with Brown's Carney Institute for Brain Science.
With its compact genome, tiny brain and a toolbox of sophisticated neurogenetic tools, the fruit fly is a powerful model organism to understand the neural substrate of behavior and investigate the underpinnings of drug reward at the molecular and cellular levels. Similar to the human mesolimbic pathway that plays a role in reward processing, the mushroom body of the fruit fly’s brain is implicated in responding to desirable and undesirable stimuli.
Glenn’s work delves into individual preference, allowing fruit flies to choose whether or not to self-administer ethanol, which is the main alcohol in beverages. In collaboration with researchers in the Kaun Lab, Glenn has identified a simple two-neuron circuit in the fruit fly’s brain that contributes to increasing ethanol self-administration. By inactivating the two neurons, she found short- and long-term changes in the fruit fly’s odor preference associated with alcohol intoxication.
“This is exciting as we now have an anatomical framework to investigate the structural and molecular changes associated with escalation of ethanol consumption,” Glenn said.
As a next step, Glenn will look for differences in neuronal structure between fruit flies that escalate and de-escalate their ethanol consumption. She is using trans-Tango, a tool developed by Brown Professor Gilad Barnea and his team, to visualize the postsynaptic targets of the cholinergic neuron. By visualizing how the two-neuron circuit structurally changes in the presence of ethanol, researchers may be able to further understand how this circuit might contribute to the escalation of ethanol self-administration, Glenn said.
“My preliminary work identifying the simple cholinergic and dopaminergic circuit with postdoctoral researcher John Hernandez may be the key to elucidating what contributes to escalation of ethanol self-administration in fruit flies,” Glenn said. “By improving our understanding of how dopamine functions alter reward pathways, we can create more effective alcohol and substance use disorder treatments.”
According to Glenn, understanding dysregulation in reward circuitry may also alleviate symptoms of dopamine-induced impulse control disorders in patients with Parkinson’s disease and other related conditions.
In addition to her work in Kaun’s lab, Glenn is also researching daily substance use behavior in young adults under the mentorship of Jennifer E. Merrill, an associate professor of behavioral and social sciences, whose work focuses on investigating the causes and consequences of alcohol misuse among young adults.
“My scientific pursuits have been possible due to the willingness, mentoring and open-door policy of Brown researchers and professors,” Glenn said. “These individuals foster an environment conducive to learning, scientific advancement and career development.”
Glenn said she will use the independent research she is conducting in the Kaun Lab as the basis for her honors thesis. Following graduation, she hopes to pursue a medical degree and a future residency in neurosurgery. She credits Brown’s Open Curriculum with allowing her to research the issue of substance abuse from different angles – and also have the time, flexibility and mentorship to dive deep into each of those areas of focus.
“The Open Curriculum enabled me to expand on my neuroscience concentration by pursuing scientific coursework spanning multiple departments," she said. "The flexibility of my concentration facilitated enrollment in social science courses to explore the history and epidemiology of substance misuse. Academic scheduling allowed me to pursue a for-credit independent study related to my research. Brown’s educational structure has been key to my ability to create a tailored education based on my future goal of pursuing medicine.”
This story was originally published by Brown University on January 25th, 2022