OHSU

Susan Ingram Osborn

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Background

My research is focused on understanding neuronal mechanisms of synaptic plasticity involved in pain and drug addiction circuits. One area of current research is focused on identifying intracellular signaling pathways involved in morphine tolerance and dependence using in vitro brain-slice recordings and in vivo behavioral assays. Our experiments focus on how mu opioid receptors (MOPrs) in the periaqueductal gray area (PAG) modulate neuronal excitability and synaptic transmission of PAG neurons. MOPrs are an integral part of the endogenous descending antinociceptive pathway that decreases pain impulses in the spinal cord. Repeated and continuous opioid administration induces neural changes in this system. We currently use whole-cell patch-clamp electrophysiological recordings, live-cell fluorescence imaging, immunohistochemical techniques, confocal microscopy, pharmacology and brain-slice and primary cultures of midbrain neurons for these studies. My collaboration with Dr. Michael Morgan at Washington State University Vancouver has been very successful in developing an integrative behavioral and cellular approach for studying mechanisms of opioid tolerance. We have set up an in vivo assay for following MOPr internalization and have identified an important role for receptor internalization in antinociception. In addition, we are finding that regulation of MOPrs (i.e. desensitization and internalization processes) is vastly different in presynaptic versus postsynaptic sites in PAG neurons. I am interested in further exploring these changes within the context of the involvement of PAG neurons in the descending antinociceptive pathway and their resulting effects on pain.

A second area of research in my laboratory is the dopamine transporter (DAT) and an associated chloride current that I identified in midbrain dopamine neurons during my postdoctoral work with Dr. Susan Amara. The DAT is one of a family of transporters that are the main targets for psychostimulants, such as amphetamine and cocaine. These transporters are also targets for therapeutic drugs for disorders including depression and attention deficit disorder. Although the transporters are primarily known for regulating extracellular concentrations of neurotransmitters through reuptake of released neurotransmitters, they have significant electrical activities as well. My recent studies determined that these transporters have a role in modulating excitability of midbrain neurons. Future studies are planned to determine the relevance of transporter-associated currents in the regulation of synaptic transmission in midbrain dopamine neurons associated with reward pathways using electrophysiology and real-time imaging of a chloride biosensor that I developed with my collaborators at the University of Pittsburgh.


Selected Publications

"Pain: Novel analgesics from traditional Chinese medicines," Current Biology (Vol: 24, Issue: 3, Page R114-R116) - 2014

"Chronic inflammatory pain prevents tolerance to the antinociceptive effect of morphine microinjected into the ventrolateral periaqueductal gray of the rat," Journal of Pain (Vol: 14, Issue: 12, Page 1601-1610) - 2013

"Columnar distribution of catecholaminergic neurons in the ventrolateral periaqueductal gray and their relationship to efferent pathways," Synapse (Vol: 67, Issue: 2, Page 94-108) - 2013

"Differential control of opioid antinociception to thermal stimuli in a knock-in mouse expressing regulator of G-protein signaling-insensitive Gαo protein," Journal of Neuroscience (Vol: 33, Issue: 10, Page 4369-4377) - 2013

"Regulation of μ-opioid receptors: desensitization, phosphorylation, internalization, and tolerance.," Pharmacological reviews (Vol: 65, Issue: 1, Page 223-254) - 2013

 

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