Project Summary
The primary training objective of the K99 phase of this K99/R00 application is to provide the candidate with
training in state-of-the-art electrophysiology techniques in preparation for a career as an independent investigator
in the field of alcohol research. The overarching hypothesis of this proposal is that decision-making malfunctions
in alcohol use disorder (AUD) are caused by concurring neural activity changes in multiple key brain regions that
serve to route the decision-making process through different circuits. To address this hypothesis, this award will
use high-density neural probes to record the electrical activity of hundreds of neurons across many brain regions
in head-fixed mice during the decision to drink. The candidate will obtain the necessary training in the use of
these neural probes to generate large neural recording data sets that can be used to directly observe changes
in the neural circuits underlying malfunctioning decision-making in AUD. To obtain this necessary training, the
candidate will work with leading researchers already using these tools in the International Brain Laboratory
collaboration and attend a training workshop. The candidate’s career development will also be furthered by
publishing results in high-impact journals, attending conferences, and attending relevant on-campus seminars.
The proposed mentoring team includes Dr. Christopher Lapish, Dr. Woody Hopf, Dr. Susan Sangha, Dr. Kenneth
Harris, and Dr. David Kareken. These individuals are experts in systems and computational neuroscience, the
neural circuitry of fear and reward, alcohol research, head-fixed mouse studies, and sex as a biological variable.
The long-standing collaborative research environment at IUPUI will provide the candidate with the necessary
resources to complete the aims as outlined in this proposal. During the end of the K99 phase of the award, the
candidate will seek out a faculty position as an independent investigator to begin at the start of the R00 phase
of the award. In this new position, the studies will expand to include the neural correlates of aversive stimuli in
order to better understand the decision to continue drinking alcohol in the face of negative consequences. This
work will lead to R01 grant applications by the candidate related to further recordings and interventions in neural
circuits to treat malfunctioning decision-making. By identifying changes in the neural circuits underlying
malfunctioning decision-making, this research will guide future studies that seek to develop novel treatments for
those people suffering from or at risk for AUD. This award will lay the foundation for an independent career in
alcohol research which has the potential to greatly improve the lives of people impacted by this disease.
