Biomedical Neuroscience Training Program
Faculty Listing

Sarah Appel PhD.
Professor
Ionic Mechanisms of Neurotransmitters, Drugs and Alcohol on
Brain Neurons

The research interests of our laboratory group are in the areas of neurophysiology and neuro-pharmacology of the mammalian brain. We study the basic electrophysiological properties of brain neurons and the ionic mechanisms which mediate the action of neurotransmitters and drugs on these neurons. Some of our studies are performed with totally submerged slices of rat brain maintained in vitro which allows stable intracellular recordings to be made from adult brain neurons with both current clamp and single-electrode voltage clamp recording. We also perform whole cell patch clamp recording from acutely dissociated catecholamine neurons. Much of our research has focussed on noradrenergic neurons of the locus coeruleus nucleus. This nucleus has extensive projections throughout the central nervous system and is involved in attention, arousal, affect and response to stress. Locus coeruleus neurons fire action potentials spontaneously in the absence of synaptic input. We have been involved in identifying and characterizing the voltage-dependent channels which underlie this "pacemaker" activity, regulate firing rate and control the shape and duration of the action potential. We have also studied the mechanisms by which the neurotransmitter gamma-aminobutyric acid and the neuromodulator adenosine inhibit these neurons. A primary area of ongoing interest in our laboratory is investigation of how alcohol affects the electrical activity of locus coeruleus neurons. We are also studying the effect of alcohol on dopaminergic neurons of the ventral tegmental area. These neurons are thought to be involved in the rewarding properties of drugs of abuse including alcohol.

Recent Publications

• Osmanovic, S.S. and Shefner, S.A. Calcium-activated hyperpolarizations in rat locus coeruleus neurons in vitro. Journal of Physiology (London) 469: 89-109, 1993.
• Pan, W.J., Osmanovic, S.S. and Shefner, S.A. Adenosine decreases action potential duration by modulation of A-current in rat locus coeruleus neurons. Journal of Neuroscience 14: 1114-1122, 1994.
• Osmanovic, S.S. and Shefner, S.A. Ethanol enhances inward rectification in rat locus coeruleus neurons by increasing the extracellular potassium concentration. Journal of Pharmacology and Experimental Therapeutics 271: 334-342, 1994.
• Pan, W.J., Osmanovic, S.S. and Shefner, S.A. Characterization of the adenosine A1 receptor-activated potassium current in rat locus coeruleus neurons. Journal of Pharmacology and Experimental Therapeutics 273: 537-544, 1995.
• Brodie, M.S., Trifunovic, R.D. and Shefner, S.A. Serotonin potentiates ethanol-induced excitation of ventral tegmental area neurons in brain slices from three different rat strains. Journal of Pharmacology and Experimental Therapeutics 273: 1139-1146, 1995
• Brodie, M.S. and Appel, S.A. The effects of ethanol on dopaminergic neurons of the ventral tegmental area studied with intracellular recording in brain slices. Alcoholism: Clinical and Experimental Research, 22:236-244, 1998.