Henry Ralston III, MD, PhD, Professor
henry.ralston@ucsf.edu
Administrative Assistant: 415-476-1861

Neuronal Organization of The Mammalian Somatosensory System

The current research interests in Dr. Ralston’s laboratory involve studies of the organization of the neural networks that serve somatic sensation, including pain, in the mammal. These investigations involve labeling of elements of neuronal networks and the subsequent examination of these neuronal populations by light and electron microscopic methods. In one series of studies, neurons of the somatosensory thalamus are recorded from, and their physiological responses to particular somatic stimuli characterized. Small numbers of these neurons can then be labeled by the iontophoretic injection of a substance, such as biocytin, that is taken up by the neurons (“juxtacellular filling”). The cells can subsequently be identified using histochemical and immunocytochemical methods and their synaptic relationships determined by light, scanning confocal and electron microscopic analysis. We study the synaptic inputs to these cells by labeling the afferent projections to the somatosensory thalamus by the transport of various tracer substances injected into other regions of the nervous system which project to the thalamus. Dr. Ralston and his colleagues have shown that such synaptic connections are plastic, in that lesions of one of the afferent pathways of the thalamus result in a reorganization of the surviving pathways as well as the intrinsic circuitry of the thalamus. This methodology is being used to examine animal models of central pain syndromes in humans, as neurosurgical thalamic recordings in patients indicate that humans with central pain states have abnormal responses of thalamic neurons that suggest altered thalamic circuitry.

Another series of studies concerns an animal model of peripheral neuropathy. Nerve injury in humans may lead to chronic, burning pain in the part of the body supplied by the damaged nerve. We are studying the spinal cord of rats that have had a partial ligation of the sciatic nerve. The animals exhibit an abnormal sensitivity to innocuous stimuli applied to the foot, and we have found that the central terminations of large diameter sciatic axons arborize abnormally into regions of the dorsal horn of the cord that they would normally not occupy. Furthermore, we have found major reductions in the gene expression and related synthesis of g-aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the central nervous system. We believe that these changes in spinal cord circuitry and neurotransmitter play an important role in the genesis of peripheral neuropathic pain in animals and in humans.

This research work is supported by a Program Project and an individual research grant from the National Institutes of Health. The laboratory is equipped to carry out a variety of experimental techniques, including single cell recording, immunocytochemistry, histochemistry, light and electron microscopy, and computer assisted reconstruction of neurons.

Complete list of Publications/PubMed

Selected Publications

Ralston, H.J., III and D.D. Ralston. (1992) The primate dorsal spinothalamic tract: evidence for a specific termination in the posterior nuclei (Po/SG) of the thalamus. Pain. 48:107-118.

Ralston, H.J. III and D.D. Ralston. (1994) Medial lemniscal and spinal projections to the Macaque thalamus: an electron microscopic study of differing GABAergic circuitry serving thalamic somatosensory mechanisms. J.Neurosci. 14:2485-2502.

Ohara, P.T., H.J. Ralston III and L.A. Havton. (1995) Architecture of individual dendrites from intracellularly labeled thalamocortical projection neurons in the ventral posterolateral and ventral posteromedial nucleus of cat. J.Comp.Neurol. 358: 563-572.

Meng, X-W, P.T. Ohara and H.J. Ralston III. (1996) Nitric oxide synthase immunoreactivity distinguishes a sub-population of GABA-immunoreactive neurons in the cat ventrobasal complex. Brain Res. 728: 111-115.

Ralston, H.J. III, P.T. Ohara, X-W Meng, J. Wells and D.D. Ralston. (1996) Transneuronal changes in the inhibitory circuitry in the macaque somatosensory thalamus following lesions of the dorsal column nuclei. J. Comp. Neurol. 371: 325-335.

Meng, X-W, P.T. Ohara and H.J. Ralston, III. (1997) Ultrastructural localization of nitric oxide synthase immunoreactivity in the cat ventrobasal complex. J. Neurocytol. 27: 833-842.

VanderHorst, V.G.J.M., E. Terasawa, H.J. Ralston III and G. Holstege. (2000) Monosynaptic projections from the nucleus retroambiguus to motoneurons supplying the abdominal wall, axial, hindlimb, and pelvic floor in the female rhesus monkey. J. Comp. Neurol. 424:251-268.

VanderHorst, V.G.J.M., E. Terasawa, H.J. Ralston III and G. Holstege. (2000) Monosynaptic projections from the lateral caudal periaqueductal gray to the nucleus retroambiguus in the rhesus monkey: implications for vocalization and reproductive behavior. J. Comp. Neurol. 424:233-250.

Ralston, D.D., P.M. Dougherty, F.A. Lenz, H.-R. Weng, C.J. Vierck and H.J. Ralston. (2000) Plasticity of the inhibitory circuitry and neuronal responses in the primate somatosensory thalamus (VB) following lesions of the dorsal column and spinothalamic pathways. Proceedings of the 9th World Congress on Pain, M. Devor, M. Rowbotham and Z. Wiesenfeld-Hallin, Eds. in, Progress in Pain Research and Management. IASP Press, Seattle. 17: 427-434.

VanderHorst, V.G.J.M., E. Terasawa, H.J. Ralston III. (2001) Monosynaptic projections from the nucleus retroambiguus region to laryngeal motoneurons in the rhesus monkey. Neuroscience. 107: 117-125.

VanderHorst, V.G.J.M., E. Terasawa, H.J. Ralston III. (2002) Estrogen receptor-alpha immunoreactive neurons in the ventrolateral periaqueductal gray receive monosynaptic input from the lumbosacral cord in the rhesus monkey. J. Comp. Neurol. 443: 27-42.

VanderHorst, V.G.J.M., E. Terasawa, and H.J. Ralston III. (2002) Axonal sprouting of a brainstem-spinal pathway after estrogen administration in the adult female rhesus monkey. J.Comp.Neurol. 454:82-103.

Ralston, H.J. III (2003) Pain, the brain, and the (calbindin) stain. J.Comp.Neurol. 459:329-333.

VanderHorst, V.G., E. Terasawa, and H.J Ralston III. (2004) Projections from estrogen receptor-alpha immunoreactive neurons in the periaqueductal gray to the lateral medulla oblongata in the rhesus monkey. Neuroscience. 125: 243-253.