Ion Channel Biophysics Unit - Division of Intramural Research
John R. Clay, Ph.D., Senior Investigator
Dr. Clay received a B.S. in Engineering Physics from Cornell University and a Ph.D. in Physics from the University of Rochester, Rochester, NY. He carried out postdoctoral work with Walter Freeman at the University of California, Berkeley, where he studied signal transduction in the olfactory cortex. He subsequently worked in the laboratory of Robert DeHaan and Lou DeFelice at Emory University in Atlanta, where he investigated ion currents underlying developmental changes in pacemaker activity in chick embryonic heart cells. His laboratory is currently investigating ionic current mechanisms which underlie neuronal bistability.
The primary interest of this lab is the switching behavior between disparate neuronal states such as the sudden onset of epileptic seizures and sporadic apnea in newborn infants, especially preterm infants. In the latter example the infant suddenly stops breathing for reasons which are not fully understood. Usually the infant spontaneously switches back to normal breathing within several seconds for reasons which are also not understood, although the apnea can be prolonged and life threatening. The central neural oscillator which controls breathing appears to have two stable states in preterm infants, one in which normal breathing occurs and one in which the oscillator is quiescent. Low level stimuli, such as electrical noise, may be the trigger which produces switching between the two stable states. We have been using single cell preparations, especially squid giant axons, to examine this behavior and other behaviors of more complicated systems. A recent finding of this work concerns the optimal stimulus required to stimulate a neuron. Rectangular current pulses are usually thought to be optimal even though they do not occur in nature. We have found that sinusoidal waveforms have greater optimality since they stimulate a neuron with less current than used in pulses. These results may have relevance to the treatment of Parkinson's disease with electrical current pulses administered by means of implantable electrodes in the vicinity of the sub-thamlamic nucleus and the globus pallidus.
Selected Recent Publications
Clay, J.R., Forger, D.B., & Paydarfar, D
Ionic mechanism underlying optimal stimuli for neuronal excitation: Role of Na+ channel inactivation, PLOS One 7(9) e45983, 2012 Full Text/Abstract
Forger, D.B., Paydarfar, D., & Clay, J.R.
Optimal stimulus shapes for neuronal excitation, PLOS Computational Biology 7, 2011, vol. e1002089, pp. 1-9. Full Text/Abstract
Determining K+ channel activation curves from K+ channel currents often requires the Goldman-Hodgkin-Katz equation., Frontiers in Cellular Neuroscience 3, Article 30, 1-6., 2009 Full Text/Abstract
Clay, J.R., Pardarfar, D., & Forger, D.B.
A simple modification of the Hodgkin and Huxley equations explains type 3 excitability in squid giant axons., J. Royal Society Interface, 2008, vol. 5, pp. 1421-1428.
Paydarfar, D., Forger, D.B., & Clay, J.R.
Noisy inputs and the induction of on-off switching behavior in a neuronal pacemaker, J. Neurophysiology, 2006, vol. 96, pp. 3338-3348.
Axonal excitability revisited, Prog. Biophys. & Mol. Biology, 2005, vol. 88, pp. 59-90.
On the persistent sodium ion current in squid giant axons, J. Neurophysiology, 2003, vol. 89, pp. 640-644.
A novel mechanism for irregular firing of a neuron in response to periodic stimulation: Irregularity in the absence of noise, . J. Computational Neurosci, 2003, vol. 15, pp. 43-51.
Selected Earlier Publications