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Marina Wolf is our Faculty Member of the Month. She is a Professor of Behavioral Neuroscience at Oregon Health & Science University and her lab is working to understand why recovering addicts are susceptible to drug cravings and relapse despite long periods of abstinence. In this blog, she talks about what inspired her to pursue a career in neuroscience and what career advice she would give to her younger self.

What does your lab study?

The goal of my lab is to understand why recovering drug addicts remain vulnerable to drug craving and relapse even after long periods of abstinence.  We study this using the ‘incubation of drug craving’ model, in which cue-induced drug craving in rats progressively intensifies (incubates) over the first weeks of forced abstinence from drug self-administration and then remains high for months. This model has translational relevance because incubation of craving also occurs in human drug users.

At present, we are focused on understanding synaptic mechanisms in the nucleus accumbens that underlie the persistence of cue-induced craving for cocaine and methamphetamine, focusing on ionotropic glutamate receptors and group I metabotropic glutamate receptors.

Excited by the groundbreaking work on glutamate receptors and LTP that was coming out at the time, I began wondering if addiction should be conceptualized as a form of aberrant but extremely powerful learning

Our workflow involves training animals to self-administer drugs, allowing varying periods of home-cage “abstinence”, testing for cue-induced drug craving and using biochemistry, electrophysiology and fiber photometry to understand the relationship between glutamate receptor plasticity and the level of drug craving. We also use primary neuronal cultures to study mechanisms that regulate glutamate receptor trafficking and function in reward-related brain regions.

What is your lab like?

My lab moved to Oregon Health & Science University (OHSU) in Portland last summer. After many happy years at Rosalind Franklin University of Medicine and Science in Chicago, I was ready for a new adventure in the Pacific Northwest!  So far, the move has been great – I’m enjoying both Portland and OHSU because they combine the diversity and opportunities of a big city/medical center with the collegiality and warmth of a small town/school.

I am a Professor in the Department of Behavioural Neuroscience, a basic science department in the medical school. The faculty share an interest in using cellular and systems-level approaches to understand brain disorders, and there is a strong cohort working on addiction.

My lab group is small right now, as a result of the recent move, but we are growing! Shown are postdocs Amanda Wunsch and Alex Kawa, along with Research Associate Jon Funke (center), in our drug self-administration lab.

What inspired your work into drug addiction and neuronal plasticity?

I had no formal training in addiction research or behavioural neuroscience.  As a PhD student and postdoc, my work focused on fundamental properties of dopamine neurons. However, as a new Assistant Professor, I was surrounded for the first time by addiction researchers. I learned about prominent theories of addiction, which focused almost exclusively on events intrinsic to dopamine neurons. Based on my past research, I thought of the dopamine system in terms of its incredible capacity for homeostasis, not as an “instigator”, so these theories were not entirely satisfying to me. Excited by the groundbreaking work on glutamate receptors and LTP that was coming out at the time, I began wondering if addiction should be conceptualized as a form of aberrant but extremely powerful learning, and if the cascade leading to addiction might depend upon glutamate and synaptic plasticity.

Science cycles up and down, but what never gets old is the satisfaction of helping students and postdocs find their way. It is wonderful to have student-mentor relationships turn into friendships.

My lab’s first behavioural experiment showed that NMDAR antagonists prevented the development of behavioural sensitization (1991), an addiction model that was approachable for newcomers to the field. We quickly incorporated biochemical and electrophysiological approaches to understand the basis for this and related observations in terms of glutamate receptor function. Believe it or not, in the 1990s, the idea that synaptic plasticity contributed to addiction was anathema to leaders in the field including journal editors. 

We had to struggle to get our work published and even then we often had to “sanitize” the language so that we were not referring explicitly to synaptic plasticity. It is amazing how far the field has come. Along the way, I’ve developed a dedication to addiction research that has two cornerstones. First, I want to help reduce the consequences of this devastating disease. Second, I believe that work in addiction models has enormous potential to reveal the rich repertoire of experience-dependent plasticity mechanisms that can be engaged in the adult brain.

What do you find rewarding about your job?

Science cycles up and down, but what never gets old is the satisfaction of helping students and postdocs find their way. It is wonderful to have student-mentor relationships turn into friendships.

Keeping up with the literature is critical to doing good science, but this is increasingly difficult as more and more things conspire to take up our time. Working on F1000Prime gives me an extra push to make it happen!

What is one piece of career advice you wish you could give to your younger self?

That would be a long conversation… But I would definitely instruct my younger self to stop ruminating! Of course, one must think through each decision or experimental plan as carefully as possible. But if things go poorly despite your best efforts (for example, the expensive piece of equipment you purchase does not prove to be very useful), let it go. Move on to the next decision.

There were some things I got right, however. I followed questions rather than techniques, and I discovered how much fun it was to have the ability to pivot my research focus if I had an exciting new idea. I read broadly and quickly learned that “innovation” is sometimes nothing more than merging two previously disparate lines of work (e.g., synaptic plasticity and addiction). Finally, I quickly developed a good scheme for the work-life balance based on a strict separation of “church and state”, i.e., when I was at work I thought about work and when I was at home I thought about my kids (until they went to bed, of course!).

What do you like about working on F1000Prime?

Keeping up with the literature is critical to doing good science, but this is increasingly difficult as more and more things conspire to take up our time. Working on F1000Prime gives me an extra push to make it happen!

How do you select your recommendations?

I consider many different types of papers. In my ideal paper, the authors would ask a clear question about the relationship between synaptic transmission and motivated behaviour, select an animal model that is sufficiently sophisticated to match the question, and then go after the answer using the most powerful techniques that are tractable in the context of that model.