Research Projects
Influence of chemical defense systems on alcohol use
Oral chemesthesis refers to the broad class of sensations evoked by chemical irritants in the mouth, like the cooling of menthol, the spiciness of chili peppers, and the burn of high-proof alcohol. This sense likely evolved as an alarm system to help mammals detect and avoid harmful substances. Despite its importance for survival and flavor preferences, the neurobiological basis of oral chemesthesis has received very little attention compared to other senses.
Our lab is working to identify the peripheral and central pathways that allow the brain to distinguish chemesthetics, such as alcohol, from taste, temperature, and touch. We've developed new ways to observe and manipulate trigeminal ganglion cells, located below the ventral surface of the brain, that were previously difficult to access. By understanding these circuits, we aim to gain insights into why some chemicals (like alcohol) are consumed despite their irritating properties, potentially leading to a new understanding of the pathophysiology of alcohol use disorder.
Past and present funding:
W. M. Keck Foundation
Whitehall Foundation
BBRF Young Investigator Award (Snigdha Mukherjee)
Circuit-based activity signatures of maladaptive decision-making
A major focus of the lab is to understand the neural mechanisms of individual differences in decision making --- that is, why some individuals develop maladaptive behaviors while others remain resilient despite similar experiences. For example, although a large portion of the population will be exposed to alcohol, only some will go on to develop an alcohol use disorder.
We develop behavioral procedures in rodents to model these phenomena, such as our Structured Tracking of Alcohol Reinforcement (STAR) framework, which allows us to quantify both alcohol intake and compulsive drinking (continued use despite negative consequences). Using these approaches, we can determine the pre-existing differences that may contribute to individual vulnerability as well as how neural circuits change with experience. By combining these models with various recording and manipulation techniques (described on the techniques page), we dissect the circuitry of maladaptive decision making.
Past and present funding:
INIA
Evelyn’s F30
R00
BBRF Young Investigator Award
R01
Cohen Innovation Fund
Mechanisms of dopamine signaling and drug action
Dopamine is critical for a wide range of behavioral processes, including cognition and motivation, and is also a primary target of many abused substances. The magnitude, timing, and duration of dopamine signaling is sculpted by a diverse array of molecular mechanisms within dopamine terminals as well as the surrounding local microenvironment. Using fast-scan cyclic voltammetry to directly measure dopamine release combined with optical and pharmacological tools to perturb this system, we explore the basic mechanisms that govern dopamine signaling kinetics. Our studies examine how these systems differ across individuals and brain regions and investigate how substances of abuse interact with dopamine circuits to alter neurotransmission and produce behavioral effects.
Past and present funding:
R01
Patrick’s F31
Cody R00
Kirsty’s F31
Suzanne’s F32
Precision medicine approaches for treating drug use disorders
An overarching drive behind the lab’s scientific inquiry is the identification of treatment strategies for drug use disorders, due to a pressing need for a greater understanding of individual differences in treatment responsivity and how to best apply precision pharmacology in a clinical setting. We have developed preclinical models of drug use which capture wide phenotypic variance across individuals and over time, mirroring phenotype dynamics in humans. The control afforded by preclinical models provides a unique avenue for assessing individual differences in treatment responsivity. By combining these models with circuit-based measures as well as peripheral and neurochemical biomarker screens, we can identify factors which predict or dictate treatment efficacy for a given individual. Our primary aim is to develop personalized therapeutic strategies rather than de novo target identification.
Past and present funding:
P60 Project
P60 Core
Non-Human primate / Cross-Species work
A major goal of our lab is to bridge discoveries from animal models to human health by identifying neural mechanisms that are conserved across species. While rodent studies provide powerful tools for understanding brain circuits, non-human primate models allow us to test how these findings translate to more complex brains and behaviors.
We develop behavioral and neurobiological frameworks that support cross-species addiction research, including the Structured Tracking of Alcohol Reinforcement (STAR) framework and the first model of intranasal drug self-administration in non-human animals. Using real-time dopamine recordings and high-density calcium imaging in non-human primates, we investigate the neural circuits underlying decision-making, addiction, and chronic alcohol exposure, with the goal of advancing basic neuroscience discoveries toward human applications.
Past and present funding:
INIA
P50 Pilot Project