835 S. Wolcott Ave., (M/C 901)
Chicago, IL 60612-7342
312-996-7620 phone
312-996-1414 fax

Sarah B. Appel, Ph.D.
(formerly known as Sarah A. Shefner)
Professor

The research interests of my laboratory are to understand the electrophysiological properties and pharmacology of dopaminergic neurons in the ventral tegmental area and noradrenergic neurons of the locus coeruleus. Our electrophysiological techniques include intracellular and extracellular recording in brain slices, whole cell patch-in-the-slice recording and cell-attached, whole cell and nystatin perforated patch clamp recording in acutely dissociated neurons. Current clamp recording is used to study the properties of the action potentials, and voltage clamp recording is used to characterize the voltage-gated ion channels in these neurons. For some time, we have focused on identifying the voltage-gated currents which contribute to the afterhyperpolarization (AHP) which follows the action potential in these cells and which paces their spontaneous firing. We have also studied the neuromodulatory actions of adenosine and the effects of ethanol on these neurons. Our studies on ethanol effects on the locus coeruleus neurons are relevant to understanding the sedative properties of ethanol and the alcohol withdrawal syndrome.

Our most recent work has focused on the dopaminergic neurons in the ventral tegmental area (DA VTA). These neurons are the cells of origin of the mesolimbic and mesocortical dopamine pathways and are involved in the rewarding properties of most drugs of abuse, including ethanol. Understanding the effect of ethanol and its mechanism of action on these neurons is crucial to understanding voluntary intake of ethanol and alcohol addiction. We have shown that acutely dissociated DA VTA neurons, stripped of all input from surrounding neurons, are robustly excited by behaviorally relevant concentrations of ethanol, strong evidence that ethanol directly excites these neurons. Current work in our laboratory combines electrophysiological and pharmacological approaches with molecular biological methods, including single cell RT-PCR, immunohistochemistry and oocyte expression to study the mechanism by which ethanol excites DA VTA neurons. We have also studied potentiation of the ethanol excitation of these neurons by serotonin, cocaine and cocaethylene.

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