On the formation and functions of the neurons in the spinal cord that project axons to the thalamus, in rodent and primate.

Abstract

Mammals and other advanced vertebrates possess a population of neurons located in the spinal cord that put forth axons to the thalamus. These cells are responsive to somatosensory stimuli and in humans are required for the normal perception of mechanical, thermal, and chemical stimuli. The studies contained in this thesis examine both the development of this pathway, called the spinothalamic tract (STT), and its physiological responses to stimuli that evoke somatosensory experiences. Experiments in adult mice show that the whole STT is made up of about 7000 cells and these are located in a pattern homologous to the STT in rat, cat and monkey. Experiments in neonatal and embryonic mice show that the axons of the STT reach the thalamus before birth. A study of the physiological characteristics of STT neurons located in the marginal zone of the spinal cord dorsal horn in the adult rat suggests that STT axons are topographically organized within the ventrobasal complex of the thalamus according to their responses to thermal stimuli. Studies in primates show that axons from the STT that project to the nuclei of the posterior thalamus are responsive to multiple modalities of somatosensory stimuli but differ from neurons projecting to VPL in some functional properties. A special focus of this thesis explores the poorly understood sensation of itch. Evidence is provided for at least two pathways for itch; one that is activated by cutaneous administered histamine and another that is activated by the protease contained within the spicules of the tropical legume cowhage. Despite this specificity for types of itch, each of these pathways is also responsive to noxious and/or innocuous mechanical, thermal and/or chemical stimuli. The population of cells that is responsive to histamine is transiently inhibited by scratching the skin during the histamine response, suggesting a mechanism for the well known relief from itch that is produced by scratching. The main conclusions from the studies in this thesis are that the STT is extant before the time of birth; that, in adults, it is a complex pathway that can contribute to the encoding of specific somatosensory sensations from cells that are responsive to multimodal stimuli.