I am interested in how the brain creates motivation to guide adaptive reward seeking, and how neural circuits that evolved to serve this function change to promote maladaptive behavioral patterns
Dopamine neuron control of conditioned cue motivation
Signaling from dopamine neurons contributes broadly to reward processes, but their function in anatomically-defined circuits is not well understood. A major focus of my research is to determine how subpopulations of dopamine neurons contribute to distinct facets of reward.
To this end, I use genetic-targeting strategies to manipulate and record activity from dopamine neurons as rats engage in behavior.
A major way dopamine neurons influence reward seeking is by modulating the value of environmental stimuli ("cues") that become associated with rewarding outcomes. Exactly how this process occurs at a neural-circuit level remains unclear. In a Pavlovian conditioning task, I found that a cue paired with optogenetic activation of dopamine neurons acquired the ability to evoke behaviors on its own, even though it was never associated with "real" reward (i.e., food or water). The topography of cue-evoked behaviors, however, differed according to the dopamine neuron subpopulation engaged. This project demonstrates that dopamine neuron activity can take the place of a natural rewards to imbue environmental cues with motivational value to drive various behaviors.
New technologies make it possible to simultaneously manipulate and measure activity from neurons based on genetic and/or anatomical identity. In these studies I use fiber photometry to record calcium activity (via GCaMP6) in dopamine neurons. This, coupled with optogenetic manipulations (via ChrimsonR), allows for assessment of cue-evoked activity in dopamine neurons during Pavlovian conditioning.
Midbrain circuit dynamics in cocaine seeking
As part of a pending K99/R00 grant from the National Institute on Drug Abuse, I am using head-mounted miniature microscopes to image calcium activity with single cell resolution in midbrain circuits. This project will identify how genetically (dopaminergic, GABAergic) and projection (striatal, thalamic) defined midbrain neurons respond to cocaine exposure, how they change with repeated drug experience, and how they are engaged by drug-associated cues to promote or suppress drug-seeking.
General Aim: Characterize serial mesostriatal circuit dynamics across cue conditioning. This project will utilize multi-site fiber photometry, optogenetic, and genetic deletion strategies in dopamine neurons to investigate the hypothesis that a progressive recruitment of ventral-to-dorsal projecting dopamine neuron signaling underlies motivational shifts in Pavlovian cue-evoked behavior.
General Aim: Characterize midbrain neuronal ensembles underlying distinct Pavlovian conditioned responses. This project will use in vivo calcium imaging to investigate the hypothesis that distinct dopamine neuronal ensembles in the ventral tegmental area encode conditioned responses that reflect cue attraction "wanting" versus cue-evoked movement invigoration.