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Uncovering the neural mechanisms mediating reward vs. aversion

Neuropsychiatric illnesses such as bipolar and substance use disorder are characterized by dysregulated motivation, for example involving excessive reward seeking or heightened risk sensitivity. Our research focuses on understanding how the brain generates motivated behavior in order to understand how dysfunction develops. We aim to identify distinct neural populations that contribute to appetitive motivation and to fear-based avoidance. In some cases, the same neural populations can flexibly switch between promoting reward to promoting aversion. We are interested in understanding how certain motivational states cause this remarkable flexibility.

 

Growing evidence suggests that many neurons within the brain's reward circuitry are incredibly diverse and some have the capacity to release multiple neurotransmitters when activated. We aim to understand how this co-release contributes to the generation of reward vs. aversion. How is neurotransmitter co-release altered in neuropsychiatric disorders such as addiction or depression?

Ongoing Projects

  • How do neurotransmitter-specific inputs to amygdala modulate incentive motivation?

  • Why does dopamine release in some limbic areas promote both reward and fear?

  • How do changes in motivational state (such as drug sensitization) alter the balance of neurotransmitter co-release within brain reward circuitry?

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Behavioral assessment of motivation

The lab uses a variety of simple and complex behavioral assays to test motivation in mice. This includes instrumental and Pavlovian conditioning tasks, intravenous drug self-administration, optical self-stimulation assays, and tests that trigger innate avoidance (i.e., looming stimulus).

Monitoring neural activity

In combination with behavioral tests of motivation, the lab applies in vivo fiber photometry and calcium sensors to monitor pathway- and cell-type specific activity in response to salient events such as the presentation of rewarding or aversive stimuli. We also use patch-clamp electrophysiology to characterize ex vivo neurotransmitter co-release within mesolimbic reward circuitry.

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Probing cell-specific neural pathways 

We utilize optogenetics and chemogenetics to directly excite or inhibit cell-defined projections within mesolimbic reward circuitry, as well as employ gene-editing tools such as CRISPR/Cas9 to understand how specific neurotransmitters contribute to appetitive vs. fear-related behaviors. 

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