Modulating neuronal and circuit function to treat disease.
Research in the Creed lab focuses on synaptic plasticity and neuromodulation within defined neural circuits in the ventral basal ganglia: the cortico-accumbal-pallidal networks involved in reward processing, learning and selection of flexible behavioral strategies.
Specifically, we ask how chronic pain and withdrawal from addictive drugs alter function of defined neural circuits, and how circuit function drives maladaptive behavior in disease states. Dopamine and endogenous opioids are neuromodulators that interact and influence plasticity throughout the ventral basal ganglia. While these transmitters are implicated in chronic pain, mood and substance use disorders, the cellular mechanisms by which they drive changes in function of neural circuits is still poorly understood.
To this end, we use a range of techniques including in vivo and patch clamp electrophysiology, genetic sequencing, functional neuroanatomy, optogenetic manipulations and behavior to study change in function in the ventral basal ganglia in models of chronic pain, mood and substance use disorders. The main goal of the lab is to leverage insight from circuit studies to develop novel neuromodulation therapies for these disorders, including deep brain stimulation (DBS) and targeted drug delivery and neurostimulation with focused ultrasound (FUS). By first establishing links of causality between neuronal and circuit adaptations and specific behavioral symptoms of disease, we can determine a rationale for targeted circuit manipulation in a disease state. We can then design novel neuromodulation paradigms and validate their efficacy in models to provide novel, effective neuromodulation therapies.
Specifically, we ask how chronic pain and withdrawal from addictive drugs alter function of defined neural circuits, and how circuit function drives maladaptive behavior in disease states. Dopamine and endogenous opioids are neuromodulators that interact and influence plasticity throughout the ventral basal ganglia. While these transmitters are implicated in chronic pain, mood and substance use disorders, the cellular mechanisms by which they drive changes in function of neural circuits is still poorly understood.
To this end, we use a range of techniques including in vivo and patch clamp electrophysiology, genetic sequencing, functional neuroanatomy, optogenetic manipulations and behavior to study change in function in the ventral basal ganglia in models of chronic pain, mood and substance use disorders. The main goal of the lab is to leverage insight from circuit studies to develop novel neuromodulation therapies for these disorders, including deep brain stimulation (DBS) and targeted drug delivery and neurostimulation with focused ultrasound (FUS). By first establishing links of causality between neuronal and circuit adaptations and specific behavioral symptoms of disease, we can determine a rationale for targeted circuit manipulation in a disease state. We can then design novel neuromodulation paradigms and validate their efficacy in models to provide novel, effective neuromodulation therapies.
Research Keywords
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Experimental TechniquesWe use a variety of experimental approaches, including:
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Lab Links |
AddressDepartment of Anesthesiology, Pain Center
Washington University School of Medicine 425 South Euclid Avenue, CSRB 5th floor, 5567 St. Louis, MO 63110 
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