Welcome to the Seal Lab

 

Our work is focused on neural circuits that mediate two neurological conditions: pain and Parkinson’s disease.  We are also developing novel therapies to treat these conditions.

 

♦  Pain

Chronic pain is a major clinical problem. Over 30% of the population suffers from one or more chronic pain conditions. Effective non-addictive treatments remain inadequate. The over-reliance on opioid-based prescription painkillers has in fact contributed to the current opioid epidemic.  Work in our lab is focused on understanding how pain signals are generated within the body and on using this information to identify novel targets and treatments for pain.  We use chemogenetic, optogenetic, electrophysiology, single cell sequencing, pharmacology, biochemistry, histology and behavior to elucidate the neural circuits underlying pain.  Our work is mainly in rodents but we are also moving the work to more clinically relevant models.   

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Dorsal horn of the mouse spinal cord showing three excitatory neuron populations important for persistent forms of pain (see Peirs and Seal, Science 2016)

 

 ♦   Parkinson’s disease

Parkinson’s disease is a neurodegenerative disorder stemming from the loss of midbrain dopamine neurons.  Loss of the neurons affects basal ganglia circuitry that modulates movement.  Our laboratory is studying a novel of form of plasticity that we discovered while in mice lacking the vesicular glutamate transporter 3.  This form of plasticity occurs in the striatum and it acts to prevent the motor impairments that arise in models of Parkinson’s disease.  We believe the mechanism may serve as a new therapeutic strategy to prolong normal motor function
in Parkinson’s patients.  Studies of this plasticity are therefore directed at understanding molecular level mechanisms and system level effects. We use chemogenetic and optogenetic approaches, electrophysiology, calcium imaging, pharmacology, biochemistry, histology and behavior.
 
DiI labeled medium spiny neuron (see Divito et al J. Neurosci. 2015)MSNimageforCoverpage1