Cristal Ahmed/East Tennessean
When trauma and addiction occur together, they can create a difficult cycle. A person who survives a traumatic event may turn to alcohol to cope with overwhelming fear and memories. But alcohol use may also interfere with processes involved in learning that previously threatening situations are now safe. In a laboratory at East Tennessee State University, Liza Wills is researching how this process works and what might eventually help break the cycle.
Her path to this work began at home. Her parents, a psychiatrist and a clinical psychologist, showed her firsthand the limitations of current treatments for patients. That experience sparked her interest in neuroscience and commitment to understanding the mechanisms of the brain.
Wills holds a doctorate in experimental psychology from ETSU and is a postdoctoral research fellow in Justin Gass’ laboratory at ETSU’s Quillen College of Medicine and the James H. Quillen VA Medical Center. She is in her fourth year using preclinical models to investigate how the brain processes fear extinction when post-traumatic stress disorder, or PTSD, and alcohol use disorder, or AUD, occur together.
Gass, who recently became the VA associate chief of staff for research, leads a lab focused on understanding the relationship between trauma and addiction and how the two can contribute to worsening treatment outcomes.
The connections between neurons are important to understanding how memories work. When a person practices the piano or rides a bike, for example, neural pathways associated with those skills are reinforced. When someone experiences trauma, the brain can form strong associations with that memory.
When the brain is repeatedly exposed to reminders of trauma in safe contexts, however, it can learn that a situation that was previously dangerous is no longer a threat. These are known as extinction memories.
People experiencing PTSD may turn to alcohol to temporarily cope with symptoms, but alcohol use can interfere with processes involved in extinction learning. Wills is studying how trauma and alcohol exposure together may affect these processes.
Her research examines how trauma and alcohol disrupt extinction memory at the level of individual brain cells. Her work focuses on the infralimbic cortex, the rodent homolog of Brodmann area 25, a brain region involved in fear extinction learning and memory recall.
Wills uses a technique called Targeted Recombination in Active Populations, or TRAP. A dual-virus system tags neurons active during extinction learning with a fluorescent protein. By measuring calcium signaling associated with extinction memories, researchers can observe which neurons are active when the brain learns that a previously dangerous context is now safe and whether those cells become active again when the memory is recalled.
In groups exposed to both trauma and chronic alcohol, Wills has observed disruptions in extinction memory formation.
“I’ve found that when you combine stress and alcohol exposure, it creates a perfect storm and damages specific brain-cell populations responsible for helping us encode safety,” Wills said.
She has presented the research at several national and international conferences and is preparing the work for publication.
Her immediate focus is on another question: Why are these specific cell populations not being properly recruited to encode extinction memories?
Her ongoing work aims to uncover the mechanisms driving the disruption, research that could eventually help scientists better understand trauma, alcohol use disorder and potential approaches to treatment.
“I believe a deeper understanding of the brain’s workings holds the key to developing novel therapeutics for psychiatric disorders,” Wills said.
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