PROVIDENCE – Call it a new, innovative drink of research: neuroscientists are exploring the neuronal pathways of fruit flies – Drosophila – to better understand the ways in which alcohol changes and modifies human synapses.

About 60 percent of all human genes and 75 percent of disease-associated genes have equivalents in Drosophila, making it an ideal platform for study – what Harvard University geneticist Stephanie Mohr has called a “living petri dish.”

Here in Rhode Island, there is a growing convergence of neuroscience research related to the impact of alcohol on the neural pathways and synapses and patterns of human behavior.

ConvergenceRI recently had the opportunity to interview Dr. Kristin Scaplen, Ph.D., Assistant Professor, Neuroscience, Department of Psychology, Executive Faculty Fellow, at the Center for Health and Behavioral Sciences at Bryant University, to talk about her cutting-edge research and its potential to change the approaches to health care delivery around alcohol-related substance abuse.

ConvergenceRI: What are the opportunities to redefine the way treatments for alcohol-related substance use are developed, based upon your research with fruit flies?
SCAPLEN: Alcohol-use can cause substantial health problems and has a devastating impact on society. Every year, 3 million deaths can be attribute to harmful use of alcohol, and excessive drinking is one of the leading causes of preventable death in the United States.

As you suggest, despite this, there are few effective treatments that 1.) Help individuals initially overcome addiction and 2.) Address their prolonged risk of relapse.

This is likely because of alcohol’s complex and far-reaching effects on the brain. The work we are conducting with fruit flies provides an opportunity to study precisely how the brain changes in the context of alcohol.

The fruit fly is the perfect model organism for this because scientists have developed genetic tools to target individual neurons within a circuit so that we can manipulate, visualize, or record their activity.

This is a resolution that we just haven’t achieved in other animal models and is thus far impossible in humans.

Memory circuits – or connections between neurons within the brain – are often modified in the context of alcohol. It is thought that this modification underlies the intense cravings that an individual experiences, which of course increases the risk of relapse.

The goal of our research is to understand how memory circuits are modified to create such enduring memories for alcohol.

If we can understand how these circuits change, we can start to ask questions like: Can we change them back? Of course, the ultimate goal is to apply what we are learning from fruit flies to more complex brains like humans and to create better treatment opportunities, but we aren’t quite there just yet.

ConvergenceRI: How much collaboration currently exists between Brown, Bryant and other research entities, such as the Janelia Research Campus, on fruit fly neural research? Can you talk about the collaboration?
SCAPLEN: Research in the fly community is incredibly collaborative. I published a paper in eLife in 2021 that was a direct result of a collaboration with scientists at Brown University, Janelia Research Campus, and Rockefeller University.

That research used genetic tracing tools to map downstream connections of a memory structure within the fly brain [See link below to study.]

At least one line of my current research takes place at Brown University in collaboration with Dr. Karla Kaun in the Neuroscience Department.

For background, I previously identified a population of dopamine neurons that are important for learning an association between odor cues and alcohol intoxication [See link below to study.]

We are using two-photon microscopy to visualize the activity of dopamine neurons as flies learn. This is powerful because much of the work in the alcohol field studies how circuits in the brain are changed post-dependence, but we have the unique opportunity to capture the precise changes that occur as the flies learn and ultimately develop preferences for cues associated with alcohol intoxication.

ConvergenceRI: How could your research potentially change the approaches for treatment and recovery? What interventions might be developed, different than what is currently being deployed?
SCAPLEN: We believe that insight into how alcohol modifies circuits in the brain is imperative to develop innovative treatment strategies that significantly improve outcomes and reduce the prolonged risk of relapse.

The prolonged risk of relapse is an important facet and one we are particularly focused on – we often call Alcohol Use Disorder a chronic relapsing disorder, because 40-60 percent of individuals treated relapse within a year of treatment and long-term relapse rates are between 20-80 percent, depending on severity.

Certainly, alcohol has far-reaching effects on the brain, but one thing that is very clear is that alcohol disrupts memory circuits resulting in enduring preferences, habitual behaviors, and persistent cravings.

Persistent cravings are thought to contribute to an individual’s prolonged risk of relapse. Our research goal is to understand precisely how memory circuits are disrupted by alcohol.

Given that circuits function similarly across species, we use fruit fly as a framework and pull out general principles for how memories for intoxication act in more complex brains, with the ultimate goal of reducing risk of relapse. But again, we have more work to do before we can get to that point.

ConvergenceRI: What opportunities exist for discussion of your research in the ongoing efforts around harm reduction in Rhode Island? For example, with the COBRE focused on brain stimulation at the Providence VA?
SCAPLEN: I assume you are referring to the COBRE Center for Neuromodulation that uses transcranial stimulation.

Like transcranial stimulation, we have ongoing projects in the lab that use optogenetics and thermogenetics – light and temperature – to precisely stimulate or inhibit neurons within a circuit and understand how their activity regulates to behavior.

As it turns out, circuits function in a remarkably similar way from flies to humans. We hypothesize they are disrupted in similar ways as well.

The difference is when we stimulate or inhibit neurons, we are doing so at the level of individual neurons, so the resolution is significantly higher in determining how neural activity, and changes in that activity, affect behavior.

ConvergenceRI: A new app has been launched at Carney at Brown called SOMA looking at the way the brain channels memories of pain. Are you familiar with this approach? What do you see as potential points of intersection with your research and SOMA?
SCAPLEN: I have! I am also co-chair of BrainWavesRI, formerly BrainWeekRI, and Dr. Petzschner’s group joined us at the Pawtucket Brain Fair this past March.

Their research investigating the perception of pain is fascinating. Certainly, chronic pain is common among patients with substance use disorders, including alcohol, as many individuals often turn to alcohol to self-medicate their pain.

There are several labs that investigate chronic pain in fruit flies, most notably Dr. Greg Neely at the University of Sydney. We aren’t currently studying this in the lab, but it’s certainly an area of interest for future directions.