- Research Associate Professor
Connections between the brainstem and spinal cord have been a major topic of my research. These linkages, among their various functions, modulate pain and set up and prepare neurons for motor commands from the cortex. My main experimental approach is to use microelectrode techniques to examine electrical activity and synaptic interactions in these neuronal circuits (1, 2). Inspired by a sabbatical year at the Miami Project some years ago, I began to focus on spinal cord injury, in particular on monoamine neurotransmitters that are critical modulators of spinal neurons. With Dr. Jacqueline Sagen, I examined how transplanted chromaffin cells alter electrical signals in pain-transmitting spinal cord cells in anesthetized rats (3), and how monoamine release by these transplanted cells is altered by injury in the host (4). Another collaboration, with Dr. Brian Noga, has focused on spinal monoamine (serotonin and norepinephrine) release by descending brainstem fibers, and especially on how their concentrations evolve on a fine scale in time and space in normal or acutely injured spinal cords (5, 6). These studies are continuing, their ultimate goal being to reverse sensory and motor deficits by transplanting monoamine-releasing cells.
Another of my interests lies in developing instrumentation and methodologies of general utility in neurophysiology. A major effort has been towards a device that combines the techniques of electrical recording and stimulation, so that a single brain electrode can “see” what it has just stimulated (7). This expands the range of possibilities in several basic and clinical tasks, including rapid, minimally invasive brain mapping, uncovering damaged or hyperexcitable brain areas and monitoring stimulus effectiveness in therapeutic deep brain stimulation. It may be of use in spinal cord diagnosis and prosthesis too, which I plan to investigate. Other R&D has been on instrumentation for electrochemical detection of monoamines with a microelectrode (voltammetry), as used in our ongoing research. This has been enhanced in various ways, for example, so that it can process simultaneous signals from eight electrodes (8), do several varieties of voltammetric measurement, and simultaneously deliver drugs and record electrical activity via the same probe (1).
Finally, taking a different approach, I have also started to explore nutritional effects on spinal function. With Dr. Walter Hargraves, a food chemist at the University of Illinois, my laboratory recently showed a major reduction in chronic pain and arthritis in mice fed on a low calorie diet (9), likely due in part to altered spinal cord mechanisms. This finding suggests that there may be valuable nutritional effects on recovery from spinal cord injury that could be exploited clinically, a question we are now pursuing.
1) Hentall, I.D., Kurle, P.J. and White, T.R. 2000. Correlations between Serotonin Level and Single-Cell Firing in the Rat's Nucleus Raphe Magnus. Neuroscience 95, 1081-1088.
2) Hentall, I.D. 2000. Interactions between brainstem and trigeminal neurons detected by cross-spectral analysis. Neuroscience, 96, 601-610.
3) Hentall, I.D., Noga, B.R. and Sagen, J. 2001. Spinal transplants of adrenal medulla block nociceptive facilitation in the dorsal horn. J. Neurophysol. 85, 1788-1792.
4) Hentall, I.D. and Sagen, J. 2000. Spinal CSF from rats with painful peripheral neuropathy evokes catecholamine release from chromaffin cells in vitro. Neuroscience Letters, 286, 95-98.
5) Hentall, I.D., Pinzon, A., Mesigil, R.P. and Noga, B.R. 2003. Temporal and spatial profiles of pontine-evoked monoamine release in the rat's spinal cord. J. Neurophysol. 89, 2943-2951.
6) Noga, B.R, Pinzon, A., Mesigil, R.P. and Hentall, I.D. 2004 Steady state levels of monoamines in the rat lumbar spinal cord – spatial mapping and the effect of acute spinal cord injury. J. Neurophysol. 92, 567-577.
7) Hentall, I.D. 2004. Detection of abnormal cerebral excitability by coincident stimulation and recording. Clin. Neurophysiol. 115, 2502-2510.
8) Noga BR, Pinzon A, Ballester B, Ospina D and Hentall ID. 2005. Serotonin concentrations in the adult rat spinal cord (SC) measured simultaneously by fast cyclic voltammetry (FCV) at several locations following microinjection or surface application. Society for Neuroscience, 31st Annual Meeting, Washington DC.
9) Hargraves, W.A. and Hentall, I.D. 2005. Analgesic effects of chronic caloric restriction in the adult mouse. Pain 114, 455-61.