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. Specifically, we ask how chronic pain, withdrawal from addictive drugs or genetic mutations alter function of defined neural circuits, and how circuit function contributes to maladaptive behavior in disease states. Dopamine and endogenous opioids are neuromodulators that interact and influence plasticity in several brain areas implicated in reward and aversion processing. However, their role in the initial wiring and subsequent pruning of neural circuits is poorly understood. 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 establish a rationale for targeted circuit manipulation in a disease state. We then design novel neuromodulation paradigms and validate their efficacy in models to provide novel, effective neuromodulation therapies.
We use a variety of experimental approaches, including:
Patch clamp electrophysiology
Deep brain stimulation and neuromodulation
Acute and chronic in vivo electrophysiology
Next generation sequencing (RNA-Seq)
Behavioral assays of decision making, reward- and depression-related behavior in mice
Neuroanatomy with viral-genetic tracing
Neuroimaging and confocal microscopy
Calcium imaging with fiber photometry
Intracranial drug delivery and optogenetic manipulations