Trainer in the Following Programs:
Molecular and Cellular Pharmacology
Neuroscience
www.anesthesia.wisc.edu/pearcelab/index.html
Awards
Betty J. Bamforth Research Professor of Anesthesiology
Research in my laboratory is focused upon synaptic inhibition in the central nervous system, and its modulation by general anesthetic agents. Although the precise mechanism of general anesthetic action remains unknown, much evidence indicates that modulation of ion channels underlying inhibitory synaptic transmission plays a key role. The basic properties of the neurotransmitter receptors involved in GABA-mediated inhibitory synaptic transmission, the molecular and cellular alterations brought about by general anesthetics, and the identities of the cells that make up functionally distinct circuits in the hippocampal cortex are areas of active investigation.
General anesthetics prolong the decay of inhibitory currents, as do other drugs that modulate the GABAA receptor, including anxiolytic, sedative-hypnotic, and anticonvulsant medications. However, the molecular mechanisms underlying this common effect may be different for different classes of agents. A primary goal of the research is to identify the effects of different types of drugs on basic molecular events, such as agonist binding, unbinding, and intramolecular transitions between metastable states including open, closed, and desenstitized states. For these experiments we employ a combination of electrophysiological recording and rapid drug application techniques, applied to both native and expressed receptors, to assess the kinetic characteristics of receptors and their modulation by drugs.
A related question under investigation is the relationship between alterations
in receptor properties (prolonged decay of the inhibitory
current) and changes in inhibitory circuit function. The preparation used for
these studies is the in vitro rat hippocampal brain slice. The hippocampus is
a cortical brain region important in learning and memory. It has been studied
intensively, so a large amount of information is available about its anatomy
and physiology. We are investigating the properties and functions of different
types of inhibitory neurons. We have identified two physiologically distinct
and anatomically segregated GABAA-mediated synaptic currents
whose properties suggest that they play distinct functional roles. We are now
studying these synapses using whole cell patch clamp techniques to learn about
how their postsynaptic receptors and other factors contribute to their distinct
physiological and pharmacological properties, including their responses to anesthetic
agents. Also, we are studying the contributions that these synapses make to
integrated circuit properties such as network oscillations, by using a combination
of physiological recording, antatomical reconstruction, and computer modeling
of the circuits involved in generating coordinated network oscillations. By
altering receptor properties, anesthetics and other drugs alter information
processing, possibly by modifying circuit oscillations, and thereby bring about
the desired effects or side-effects of these clinically important agents.
Selected Publications:
Postdoctoral Positions
Postdoctoral Positions:
Two postdoctoral positions are open to study synaptic transmission and postsynaptic receptor properties.Specific problems include:
1. Study of molecular transitions of the GABAA receptor that occur with channel gating in response to binding of agonist and modulators.
2. Changes in inhibitory circuit function in response to anesthetic agents, particularly with regard to interactions between distinct inhibitory circuits.Candidates must have a strong background in cellular or molecular neuroscience, and at least two publications in major basic science journals.
Please send curriculum vitae and names of three references to:
Robert A. Pearce, M.D., Ph.D.
Betty J. Bamforth Research Professor of Anesthesiology
University of Wisconsin
1300 Univ. Ave.
Madison, WI 53706
tel. 608-263-4429
fax. 608-262-5558
rapearce@facstaff.wisc.edu