Project Summary/Abstract
Candidate: My long term goal is to become an independent investigator running an interdisciplinary and
collaborative research team to understand the mechanisms underlying the effects of medications and drugs of
abuse on intra/interconnected brain circuits . Specifically, my interests surround understanding how cholinergic
interneurons (ChAT) regulate the activity of nicotinic acetylcholine receptors (nAChRs) in the local circuitry of
the nucleus accumbens (NAc), thereby underlying sex differences in dopamine signaling associated with reward
and motivated behavior. I have a strong background in electrophysiology and pharmacology, and propose to be
trained in optogenetics, behavioral pharmacology, and in vivo fiber photometry to round out my training. This will
provide me with the skills to produce high impact publications and successful R01 submissions. I received my
PhD in April of 2017 and this is currently my third year of postdoctoral research training.
Training: In addition to Dr. Calipari, I have an advisory committee of experts in academic research who will
provide the necessary training and guidance to accomplish this proposal. Dr. Barnett, is the Vice-chair of and a
Professor in the Department of Pharmacology and Dr. McCabe is the Director of the Office of Postdoctoral
Affairs. Outside of the committee, we have identified, courses, seminars, and meetings to provide further
technical training, presentation experience, responsible conduct in research, and the necessary skills
(negotiations, tenure, laboratory management, etc.) to transition to independence.
Research: Substance use disorder (SUD) is a chronic, recurring brain disease characterized by significant
dysfunction in reward-seeking behavior. A large body of work has focused on understanding the neural
mechanisms in the brain’s reward circuitry, yet these studies have overwhelmingly focused on male subjects.
Epidemiological evidence shows that women represent a particularly susceptible population to SUD, yet the
mechanisms in the brain that underlie sex differences in reward and motivation are largely unknown. The neural
control of reward is dependent on dopamine release in the NAc that is subject to heavy modulation by ChAT
signaling through nAChRs; a process that is essential to encoding information about environmental reward
predictive cues. My preliminary data show fundamental sex differences in the regulation of dopamine release
via nAChRs, yet to date, it is not known how this process occurs, what factors influence this effect, and how this
relates to motivated behavior. The overall goal of this proposal is to define sex-specific circuit-based
mechanisms governing sex differences in reward processing. By using voltammetry techniques along with
pharmacology, behavioral analysis, and in vivo dopamine recording, I anticipate being able to expand our
understanding of the sex differences in ChAT regulation of nAChR modulation of dopamine release underlying
reward learning. The successful completion of this proposed project has the potential to inform the development
of better and more effective pharmacotherapies to counter neurological disease states in women.
