Robert A. Pearce

Inhibitory Synaptic Transmission, Hippocampal Function, and Mechanisms of Anesthetic Action

E-mail: rapearce@wisc.edu

Research Strengths: Membrane Excitability and Synaptic Transmission, Neural Circuits

Research in my laboratory is focused on understanding how anesthetics and other drugs that target GABA receptors control memory formation. Using hippocampal brain slice preparations and multichannel in vivo recordings from the hippocampus of genetically altered mice, we are investigating how inhibitory circuits found in this part of the brain support and control network activity. We are particularly interested in identifying the molecular components and functions of different types of synapses that are found on the dendrites of pyramidal neurons and interneurons, and in determining their roles in generating or controlling complex circuit responses, including rhythmic activity patterns such as theta and gamma 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:

• Perouansky, M., H. Hentschke, M.G. Perkins, and R.A. Pearce. 2007. Amnesic concentrations of the non-immobilizer 1,2 dichlorohexafluorocyclobutane (F6, 2N) and isoflurane alter hippocampal θ-oscillations in vivo. Anesthesiology 106:1168-1176.
• Benkwitz, C., M. Liao, M.J. Laster, J.M. Sonner, E.I. 2nd., and R.A. Pearce. 2007. Determination of the EC50 amnesic concentration of etomidate and its diffusion profile in brain tissue: implications for in vitro studies. Anesthesiology 106: 114-123. [PDF]
• Hardie, J.B. and R.A. Pearce. 2006. Active and passive membrane properties and intrinsic kinetics shape synaptic inhibition in hippocampal CA1 pyramidal neurons. Journal of Neuroscience 26: 8559-8569. [PDF]
• Boileau, A.J., R.A. Pearce, and C. Czajkowski. 2005. Tandem subunits effectively constrain GABAA receptor stoichiometry and recapitulate receptor kinetics, but are insensitive to GABARAP. Journal of Neuroscience 25: 11219-11230. [PDF]
• Zarnowska, E.D., R.A. Pearce, A. Saad, and M. Perouansky. 2005. The ?-subunit governs the susceptibility of recombinant GABAA receptors to block by the non-immobilizer 1,2-dichlorohexafluorocyclobutane (F6, 2N). Anesthesia and Analgesia 101: 401-406. [PDF]
• Gredell, J.A., P.A. Turnquist, M.B. MacIver, R.A. Pearce. 2004. Determination of diffusion and partition coefficients of propofol in rat brain tissue: implications for studies of drug action. British Journal of Anaesthesia 93: 810-817. [PDF]
• Mody, I., and R.A. Pearce. 2004. Interneuron diversity series: Diversity of inhibitory neurotransmission through GABAA receptors. Trends in Neuroscience 27: 569-575. [PDF]
• Benkwitz, C., M.I. Banks, , and R.A. Pearce. 2004. Influence of GABAA receptor ?2 splice variants on receptor kinetics and isoflurane modulation. Anesthesiology 101: 924-936. [PDF]
• Perouansky, M. and R.A. Pearce. 2004. Effects on synaptic inhibition in the hippocampus do not underlie the amnestic and convulsive properties of the non-immobilizer 1,2 dichlorohexafluorocyclobutane (F6). Anesthesiology 101: 66-74. [PDF]