Laboratory of Developmental Neurobiology, NIH
Ph.D. (Major: Experimental Psychology-Physiological)
University of Arkansas, Fayetteville
M.A. (Major: Experimental Psychology-Physiological)
University of Arkansas, Fayetteville
B.S. (Major: Chemistry)
University of Arkansas, Fayetteville
Assistant Professor, Department of Anatomy and Cell Biology,
Oklahoma State University Center for Health Sciences (OSU-CHS),
Assistant Professor, Department of Neurobiology, Pharmacology & Physiology,
The University of Chicago,
Senior Staff Fellow, Laboratory of Cellular & Molecular Neurophysiology,
National Institutes of Health
IRTA Postdoctoral Fellow, Laboratory of Developmental Neurobiology,
National Institutes of Health
Research Assistant, Department of Psychology,
University of Arkansas
- American Association for the Advancement of Science
- Society for Neuroscience
Honors & Awards
- Fellow, Winter Conference on Brain Research, 1996
- Lynn Waite Dunlap Creativity in Research Prize, University of Arkansas, 1987
- Charles W. Oxford Scholar, University of Arkansas, 1985-86
- National Science Foundation
- Journal of Neuroscience
- Journal of Neurophysiology
- Molecular Pharmacology
- National Institutes of Health
NIH 1R01NS36250: "AMPA receptor expression and selective neuronal death", Principal Investigator Dr. James Brorson, collaborating investigator (10% effort).
American Heart Association, Scientist Development Grant: "Proton modulation of AMPA receptors in synaptic transmission and ischemia", $260,000.
Brain Research Foundation
Graduate Student Supervision
- Eva Ihle, Ph.D. awarded December 1997, "The Role of Extracellular Protons in Regulating Fast Excitatory Synaptic Transmission Through Modulation of AMPA-Preferring Glutamate Receptors".
- Undergraduate, "Exploring the Brain", 1997-2000
- Graduate, "Fundamentals of Modern Pharmacology", 1995-1999
- Graduate, "Neuroanatomy" and "Neurophysiology", selective lectures, 1995-1998
- Graduate, "Molecular Neurobiology and Pharmacology II", selective lectures, 1995, 1996
Representative Publications & Presentations
Original Peer-Reviewed Articles
Stripling, J. S., Patneau, D. K., and Gramlich, C. A. (1988). Selective long-term potentiation in the pyriform cortex. Brain Research 441, 281-291.
Patneau, D. K., and Mayer, M. L. (1990). Structure-activity relationships for amino acid transmitter candidates acting at N-methyl-D-aspartate and quisqualate receptors. Journal of Neuroscience 10, 2385-2399.
Patneau, D. K., and Mayer, M. L. (1991). Kinetic analysis of interactions between kainate and AMPA: Evidence for activation of a single receptor in mouse hippocampal neurons. Neuron 6, 785-798.
Vyklicky, L., Jr., Patneau, D. K., and Mayer, M. L. (1991). Modulation of excitatory synaptic transmission by drugs that reduce desensitization at AMPA/kainate receptors. Neuron 7, 971-984.
Patneau, D. K., and Stripling, J. S. (1992). Functional correlates of selective long-term potentiation in the olfactory cortex and olfactory bulb. Brain Research 585, 219-228.
Patneau, D. K., Mayer, M. L., Jane, D. E., and Watkins, J. C. (1992). Activation and desensitization of AMPA/kainate receptors by novel derivatives of willardiine. Journal of Neuroscience 12, 595-606.
Patneau, D. K., Vyklicky, L., Jr., and Mayer, M. L. (1993). Hippocampal neurons exhibit cyclothiazide-sensitive rapidly desensitizing responses to kainate. Journal of Neuroscience 13, 3496-3509.
Partin, K. M., Patneau, D. K., Winters, C. A., Mayer, M. L., and Buonanno, A. (1993). Selective modulation of desensitization at AMPA versus kainate receptors by cyclothiazide and concanavalin A. Neuron 11, 1069-1082.
Patneau, D. K., Wright, P. W., Winters, C., Mayer, M. L., and Gallo, V. (1994). Glial cells of the oligodendrocyte lineage express both kainate- and AMPA-preferring subtypes of glutamate receptor. Neuron 12, 357-371.
Gallo, V., Patneau, D. K., Mayer, M. L., and Vaccarino, F. (1994). Excitatory amino acid receptors in glial progenitor cells: molecular and functional properties. Glia 11, 94-101.
Partin, K. M., Patneau, D. K., and, Mayer, M. L. (1994). Cyclothiazide differentially modulates desensitization of AMPA receptor splice variants. Molecular Pharmacology 46, 129-138.
Fleck, M. W., Bahring, R., Patneau, D. K., and Mayer, M. L. (1996). AMPA receptor heterogeneity in rat hippocampal neurons revealed by differential sensitivity to cyclothiazide. Journal of Neurophysiology 75, 2322-2333.
Stripling, J.S., and Patneau, D. K. (1999). Potentiation of late components in olfactory bulb and piriform cortex requires activation of cortical association fibers. Brain Research 441, 281-291.
Vandenberghe, W., Ihle, E.C., Patneau, D.K., Robberecht W., Brorson J.R. (2000). AMPA receptor current density, not desensitization, predicts selective motoneuron vulnerability. Journal of Neuroscience 20, 7158-66.
Ihle, E.C., Patneau, D.K. (2000). Modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor desensitization by extracellular protons. Molecular Pharmacology. 58, 1204-12.
Stripling, J. S., and Patneau, D. K. (1990). Seizure mechanisms in the piriform cortex. In Juhn A. Wada (Ed.), Kindling 4 (pp. 45-57). New York: Plenum.
Mayer, M. L., Vyklicky, L., Jr., and Patneau, D. K. (1990). Glutamate receptors in cultures of mouse hippocampus studied with fast applications of agonists, modulators and drugs. In Y. Ben-Ari (Ed.), Excitatory Amino Acids and Neuronal Plasticity (pp. 3-11). New York: Plenum.
Mayer, M. L., Vyklicky, L., Jr., Benveniste, M., Patneau, D. K. and Williamson, L. (1991). Desensitization at NMDA and AMPA-kainate receptors. In H. Wheal and A. Thompson (Eds.), Excitatory Amino Acids and Synaptic Function (pp. 123-140). New York: Academic Press.
Mayer, M. L., Benveniste, M., and Patneau, D. K. (1991). NMDA receptors: Physiological studies with divalent cations and competitive antagonists. In A. P. Kozikowski (Ed.), Neurobiology of the NMDA Receptor: From Chemistry to the Clinic (pp. 41-66). New York: VCH.
Mayer, M. L., Benveniste, M, Patneau, D. K., and Vyklicky, L., Jr. (1992). Pharmacologic properties of NMDA receptors. In Ann. N. Y. Acad. Sci.: Neurotoxins, pp. 341-355.
Mayer, M. L., Patneau, D. K., and Vyklicky, L., Jr. (1992). Desensitization, drugs and synaptic transmission at AMPA/kainate receptors. In R. P. Simon (Ed.), Excitatory Amino Acids, 9, Fidia Research Foundation Symposium Series, 125-131.
Mayer, M. L., Benveniste, M. and Patneau, D. K. (1994). NMDA receptor agonists and competitive antagonists. In G. L. Collingridge and J. C. Watkins (Eds.),The NMDA Receptor, 2nd Edition (pp.132-146). New York: Oxford University Press.
Selected Meeting Abstracts
Patneau, D. K., and Stripling, J. S. (1985, October). Functional correlates of long-term potentiation in the pyriform cortex. Fifteenth Annual Meeting of the Society for Neuroscience, Dallas, Texas. (Soc. Neurosci. Abstr. 11: 780).
Patneau, D. K., and Stripling, J. S. (1988, November). Circuitry and synaptic mechanisms underlying selective long-term potentiation in pyriform cortex. Eighteenth Annual Meeting of the Society for Neuroscience, Toronto, Canada. (Soc. Neurosci. Abstr. 14: 1188).
Patneau, D. K., and Stripling, J. S. (1989, November). Do NMDA receptors participate in normal synaptic transmission in the piriform cortex? Nineteenth Annual Meeting of the Society for Neuroscience, Phoenix, Arizona. (Soc. Neurosci. Abstr. 15: 929).
Patneau, D. K., and Mayer, M. L. (1990, February). Activation of NMDA and quisqualate receptors by endogenous excitatory amino acids. Thirty-fourth Annual Meeting of the Biophysical Society, Baltimore, Maryland. (Biophysical Journal 57: 121a).
Patneau, D. K., Winters, C. A., Vyklicky, L., Jr., and Mayer, M. L. (1990, October). Evidence that kainate responses and rapidly-desensitizing quisqualate responses are mediated by the same receptor. Twentieth Annual Meeting of the Society for Neuroscience, St. Louis, Missouri. (Soc. Neurosci. Abstr. 16: 619).
Patneau, D. K., Mayer, M. L., Jane, D. E., and Watkins, J. C. (1991, November). Novel willardiine derivatives exhibit varying degrees of desensitization at AMPA/kainate receptors. Twenty-first Annual Meeting of the Society for Neuroscience, New Orleans, Louisiana. (Soc. Neurosci. Abstr. 17: 1166).
Patneau, D. K., Vyklicky, L., Jr., and Mayer, M. L. (1992, October). Cyclothiazide modulates excitatory synaptic transmission and AMPA/kainate receptor desensitization in hippocampal cultures. Twenty-second Annual Meeting of the Society for Neuroscience, Anaheim, California. (Soc. Neurosci. Abstr. 18: 248).
Patneau, D. K., and Mayer, M. L. (1993, November). Structure-activity analysis of benzothiadiazines that modulate desensitization at AMPA-preferring receptors. Twenty-third Annual Meeting of the Society for Neuroscience, Washington, D.C. (Soc. Neurosci. Abstr. 19: 279).
Patneau, D. K., Partin, K. M., and Mayer, M. L. (1994, November). Cooperativity between binding of cyclothiazide and agonists underlies differential modulation of AMPA receptor splice variants. Twenty-fourth Annual Meeting of the Society for Neuroscience, Miami, Florida. (Soc. Neurosci. Abstr. 20: 484).
Patneau, D. K. and Ihle, E. C. (1996, November). Proton modulation of AMPA-preferring glutamate receptors. Twenty-sixth Annual Meeting of the Society for Neuroscience, Washington, D.C.. (Soc. Neurosci. Abstr. 22: 1538).
Patneau, D. K. and Ihle, E. C. (1997, October). Kinetic analysis of proton modulation of AMPA-preferring glutamate receptors. Twenty-seventh Annual Meeting of the Society for Neuroscience, New Orleans, Louisiana. (Soc. Neurosci. Abstr. 23: 1205).
Patneau, D. K. and Ihle, E. C. (1998, November). Molecular composition of AMPA receptors affects their sensitivity to modulation by protons. Twenty-eighth Annual Meeting of the Society for Neuroscience, Los Angeles, CA. (Soc. Neurosci. Abstr. 24: 97).
Patneau, D. K. and Ihle, E. C. (2001, May). Modulation of AMPA Receptor Desensitization By Protons. American Heart Association Research Symposium, Dallas, Texas.
Major Research Interests
Our laboratory is interested in how the functional properties of the AMPA subtypes of glutamate receptor are regulated and modulated at the molecular and cellular level. These receptors mediate fast excitatory synaptic transmission in the mammalian brain via ionotropic receptor-channels that open in response to binding of the neurotransmitter glutamate. Glutamate receptors are critical for the normal development and function of the nervous system and for the processes underlying learning and memory. Glutamate receptors have also been implicated in the etiology of several pathological conditions, including Alzheimer's, Huntington's and Parkinson's diseases, amyotrophic lateral sclerosis, epilepsy and stroke.
We utilize a combination of pharmacological, physiological and molecular techniques in the study of glutamate receptors in two different preparations. Native glutamate receptors are studied in primary cultures of neurons dissociated from rat brain, and recombinant receptors of varying molecular composition are transiently expressed in a human embryonic kidney cell line (HEK293). Electrophysiological recordings are made in both the whole-cell and nucleated outside-out patch configurations. Agonists and drugs are applied with ultra-rapid perfusion techniques that permit kinetic analysis of receptor activation, deactivation and desensitization from macroscopic responses.
One striking functional characteristic of AMPA receptors are their rapid (1-10 ms) and almost complete desensitization (95-99%); this desensitization is an important factor controlling the efficacy of excitatory synaptic transmission. My postdoctoral research was seminal in developing a model that explained the agonist-dependence of AMPA receptor gating and desensitization. My current research is focused on developing a comparable understanding of modulation of gating and desensitization by both exogenous and endogenous factors. Descriptions of the three major thrusts of my current research follow.
- Proton modulation of AMPA receptors in synaptic transmission & ischemia, funded by the American Heart Association. This research project examines the effects of variations in extracellular pH on the function of AMPA receptors. The specific aims are to:
- Identify the mechanism(s) mediating proton modulation of native AMPA receptors.
- Demonstrate that receptor subunit/isoform composition determines proton sensitivity of AMPA receptors.
- Characterize the physiological and pathophysiological conditions under which protons modulate AMPA receptor function.
- AMPA Receptor Expression and Selective Neuronal Death, in collaboration with Dr. James Brorson of University of Chicago. This project examines why certain types of neurons, including motor neurons and cerebellar Purkinje cells, are particularly vulnerable to excitotoxicity mediated by AMPA receptors. These experiments will determine whether these cells possess AMPA receptors with unique functional properties and/or molecular compositions that make them selectively vulnerable.
- Allosteric modulation of AMPA receptors. The development of therapeutic agents for disorders in which glutamate receptors have been implicated is complicated by the essential role of these receptor-channels in normal brain function. The most promising targets on the AMPA subtypes of glutamate receptor are allosteric sites that modulate receptor activation by glutamate. Several drugs exerting allosteric effects on the function of the AMPA receptor have been identified in the past decade. They appear to act through one of two sites on the receptor, a non-competitive inhibitory site or a positive site that can reduce AMPA receptor desensitization.
This project focuses on two fundamental aspects of determining mechanism of action of these drugs that have been relatively unexplored. The first is whether the binding and/or effect of modulatory drugs is dependent on the conformational state of the AMPA receptor. The second related aspect is the determinants of cooperativity between the binding sites for agonist and modulator.