Five Questions With…
Andrew Holmes, Ph.D. Senior Investigator, Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism
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You are the senior investigator of the National Institute on Alcohol Abuse and Alcoholism’s (NIAAA) Laboratory of Behavioral and Genomic Neuroscience. How would you describe the work of your laboratory and the importance of such basic science in helping us to understand addiction and alcohol’s effects on health?
My lab’s work seeks to learn more about the core mechanisms through which the brain recognizes, learns about, and effectively responds to challenges that organisms encounter when navigating their world to fulfill basic needs. This includes needs such as obtaining food and avoiding danger. These capabilities are often compromised to some degree in neuropsychiatric conditions, including alcohol use disorder (AUD). Hence, our ultimate objective is to be able to better understand the differences in the physiological processes of individuals suffering from these conditions, with a view to developing new and improved ways to alleviate their distress.
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What do you consider your laboratory’s most significant research accomplishments?
We have been fortunate to have contributed to the field in a number of areas that turned out to be convergent with what others have reported since. An early observation we made was that stress and alcohol both have detrimental effects on the structure and function of the prefrontal cortex, an area of the brain responsible for executive functions, such as making decisions and regulating emotions. We’ve also identified specific circuitry in the brain through which communication between the prefrontal cortex and another hub for emotional recognition, the amygdala, is critical for tamping down fear and controlling compulsive alcohol-seeking behaviors. More recently, we’ve begun to shed light on how neurons in these brain regions exhibit organized patterns of activity that may reflect how the brain “represents” memories and associated emotional states, such as fear.
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What projects are you currently working on?
The lab is currently working on a number of projects broadly related to clarifying the neural circuit mechanisms underlying behavioral processes relevant to AUD, such as the regulation of responses to threats and the control of compulsive-like behaviors. This is a particularly exciting time to be doing neuroscience of this kind because of the availability of technologies that allow us to monitor and manipulate the brain (e.g., by optically controlling neuronal activity), often with unprecedented precision. Our current research aims to leverage these new technologies to reveal new insights into long-lasting questions about the role of brain systems in orchestrating complex behaviors, such as decision-making in the face of risk.
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As a senior investigator, you mentor young scientists. In what ways do you find NIAAA’s intramural research program to be well-suited as a training ground for the next generation of alcohol researchers?
The facilities and broad, rich intellectual environment of NIAAA’s intramural program provide a vibrant place for ambitious young scientists to immerse themselves in basic, translational, and clinical alcohol-related research. The program offers an excellent “sandbox” opportunity to learn and grow, and in many ways, provides a unique place to be exposed to and become experienced in state-of-the-art research in the field. This is further enhanced by an active community, often organized and led by trainees themselves, that enables trainees to share their work with peers and the wider National Institutes of Health (NIH) intramural program. My advice to current NIAAA trainees is—even on those tougher days when your experiments don’t work—to enjoy your time at this special place. Once you move on in your career, I bet you’ll look back on your NIH days fondly!
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Your work focuses on understanding the causes of AUD and comorbid neuropsychiatric conditions, such as stress, trauma, and anxiety disorders. What led you to this field?
From my earliest days as an undergraduate psychology student, I have been intrigued by why it is we differ in the way we deal with the inevitable stressors that life throws at us, sometimes by turning to alcohol and the adverse consequences that it has the potential to bring. As a trainee, I also learned that science has the potential not only to help us understand this variation at the level of the brain, but in the process of increasing this understanding, to point to ways in which the deleterious effects of stress and drinking can be therapeutically alleviated. In the years since, the importance and urgency of this work has been brought into focus by the growing burden of stress-related conditions and AUD that we see around the world.
