Our Spotlight Neuroscientist of the Month of March 2019 was Dr. Mahler, a Neurobiology and Behavior assistant professor in the School of Biological Sciences at UCI. Dr. Mahler’s research focuses on understanding the effects of dopamine on the neurological centers in the human brain that control nicotine and alcohol addiction. His team seeks to explore how these processes relate to motivated behaviors and psychiatric disorders. The main focus of his lab is to use rats as tests subjects in order to dissect the neural circuits involving reward and addiction-related psychological processes. The guiding research questions of the lab are how pathways underlie specific behaviors in relation to addiction, which neurons seem to be involved in these circuits, and how the circuits interact with each other. After we read two of Dr. Mahler’s research journals, we discussed them in depth in order to have intellectual background and questions prepared for his colloquium. We were also given the opportunity to have lunch with him and tour his lab.
To further deepen our understanding about the mesolimbic circuits of reward, especially the roles of addictive drugs such as cocaine in this circuit, we read two of Dr. Mahler’s published articles and discussed the various models involved in this circuit and the function of ventral tegmental area (VTA) on cocaine addiction and relapse. The first paper mainly outlines the models and procedures to simulate cocaine addiction and relapse, analyzes the circuits involved in relapse risk and eventually develops therapeutic strategies to prevent drug addiction and relapse. A few examples of the models are the cocaine self-administration, where rodents are trained to self-administer cocaine by pressing a lever (operant response), and reinstatement, where rodents are primed with a small dose of cocaine or exposed to different cues and stressors that trigger relapse. The second paper expands on this research, with more statistical analysis of the tests. Dr. Mahler and his colleagues tested rats with different combinations of cocaine injections and levers for self-administration and with various time intervals between respective injections. The researchers analyzed the effects of Chemogenetic Manipulations of the VTA during specific tests of dopamine (DA) reinforcement as well as the effects of cocaine-seeking behavior. Basically, when VTA DA neurons were stimulated, rats wanted less cocaine but worked harder to obtain it. Conversely, during inhibition of DA neurons, rats wanted more cocaine but were less likely to work hard to obtain it. These results indicate that VTA DA neurons are involved in both the subjective reinforcing, and motivational activating effects of cocaine, instead of playing any single role in reward. Ultimately, these experiments led to new potential approaches to treat addiction.
During the colloquium hosted by Dr. Mahler, we were able to listen to him speak about his research and his journey to becoming the neuroscientist he is today. He began his presentation by asking us about our career goals and interests, and then shared his college experience. Dr. Mahler, with a bachelor’s degree in psychology, applied to several graduate programs but in a sad turn of events, got denied from all of them. Fortunately, one school transferred his application to a terminal master’s program which then landed him in Chicago. There, he joined the lab of Harriet de Wit, a human psychopharmacologist. Through this lab, he was introduced to what would be the topic of his thesis: discovering the role of dopamine in smoking craving. To this day, he attributes de Wit as a major key component to what led him to his current research. As he continues studying the brain, and the effects of addiction, he touches on relapse and what contributes to it. Stress and priming doses which are the phenomenons of one alcoholic drink at your friend’s wedding, can cause you to relapse, as well as conditioned cues, passing by the bar you once used to drink at. This, Mahler explains, helps us to understand addiction and how to better control it. He hopes that by studying the behavior of rats and the effects of DREADDS, we are able to gain a greater understanding of the brain’s response and relate that to humans. By doing so, we bring science one step closer to decreasing the rates of addiction.
Mitch Farrell, a current graduate student of Dr. Mahler’s lab, generously hosted a tour of the lab. During the walk-around, he introduced us to the different tools that they use in their lab including a mice brain slicer as well as needles used for administering the drugs to the rats. It was a great opportunity to learn about the many facilities that held their instruments which is useful for understanding the differences that occur in mice’s brain due to using drugs. Mitch then walked us over to a high quality microscope which was connected to a computer. He explained that by using this tool, they are able to take microscopic pictures of different areas of mice brain based on their research. Being able to view how mouse brain areas look like in such high quality pictures was a fascinating experience. He proceeded by guiding us into the surgery room, a place in which they put microchips or other important things into the brain of the mouse. It is important to note, that by doing that they are able to monitor and record the brain activity of the mouse anytime based on the research that they are doing on the animal. Later we were able to see the actual activity that each mouse would do using skinner-like boxes and applying the several tasks they had on hand. Being able to view the environment and have Mitch break down the various tools used in the research papers, was a great way to tie in all the knowledge we had acquired from the past events. In addition, it gave us a great opportunity to have an overview of how they actually perform each of the tasks that we read in their paper.
Aside from discussing his research, Dr. Mahler shared some insightful tips on applying for a research position at UCI during our luncheon. Dr. Mahler first mentioned that students should get in touch with the personal investigator (PI) of the lab by sending an email and/or attending the PI’s office hours, and that they should show interests and passion on the lab’s work and goals. Oftentimes, the PI would offer students a volunteer position first, prior to getting the research position, or require the student to dedicate some number of hours to be accustomed to the lab and learn the techniques. For example, Dr. Mahler requires students to commit ten hours a week on a project in his lab. As we enjoy our pizzas and turkey roll ups, Dr. Mahler also explained one of the perks in academia: travelling. Dr. Mahler has travelled domestically and internationally for conferences, symposiums, etc. throughout his career, most of which he had experienced a great time. Dr. Mahler even reassured us that we can squeeze in some leisure time, even though these trips are meant for business. Furthermore, Dr. Mahler walked us through the different funding/grant opportunities for graduate students and postdocs. Dr. Mahler talked about the National Science Foundation’s Graduate Research Fellowship Program (“career grant”) and the Kangaroo (K99/R00) grant as one of the many grants that graduate students and postdocs could apply for respectively.
Towards the end of our journey with our Spotlight Neuroscientist, Dr. Mahler advised us to “hang in there” whether we are aiming for academia, medical school, and other interests. Although the direction of our paths may change, it is okay to follow that road and embark on that new adventure. We just have to keep in mind that “persistence is mandatory” in reaching our ultimate destinations or goals.