Lamina I and Homeostasis

点击翻译按钮获取中文摘要

Ascending inputs to the brainstem from the spinal cord are critical for the control of homeostatic (pre-autonomic) functions, such as cardiovascular and respiratory responses to noxious or thermal stimuli that challenge the stable physiological condition of the body. It has been recognized for over 30 years that small-diameter (A-delta and C-fiber) afferent inputs generate powerful somato-autonomic reflexes in the brainstem, but there is still very little information available regarding the spinobulbar neurons that carry such activity to homeostatic brainstem integration sites. Neurons in lamina I of the superficial dorsal horn that receive direct - delta and C-fiber are the major source of spinal input to the brainstem. We have shown in prior work that lamina I neurons project to the homeostatic regions of the brainstem. New evidence suggests that lamina I spinobulbar neurons are unique population of lamina I neurons that has never been studied before. The goal of this project is to discriminate lamina I spinobulbar neurons anatomically and physiologically. In anatomic studies, we will (Aim 1) use retrograde labeling to identify lamina I and other spinal neurons that project to particular homeostatic sites in the brainstem and to verify that lamina I and other spinal neurons that project to particular homeostatic sites in the brainstem and to verify that lamina I spinobulbar an spinothalamic neurons are distinct (using double-labeling). In physiologic studies, we will (Aim 2) record and characterize single lamina I spinobulbar neurons, using antidromic activation and natural cutaneous and deep somatic stimulation, and differentiate them from spinothalamic neurons. In addition, we will (Aim 3) stimulate the anterior hypothalamus and the periacqueductal gray, two pre-autonomic control sites that drive sympathetic vasoconstrictor output, in order to determine whether descending homeostatic controls differentially modulate the activity of spinobulbar and spinothalamic lamina I neurons. Using protocols that we have refined in experiments in cats (which nonetheless have fundamental neuroanatomical differences from primates), these experiments will obtain data in macaque monkeys that will be directly relevant to human physiology. Preliminary evidence strongly indicates that these experiments will confirm the central hypotheses that lamina I spinobulbar neurons are a distinct population of neurons. These experiments will differentiate and characterize for the first time the ascending modality-selective spinal neurons that carry small- diameter A-delta and C-fiber afferent inputs to homeostatic and pre- autonomic integration mechanisms in the brain stem. The fundamental knowledge will provide new opportunities for explaining maladaptive homeostatic responses to somatic physiological changes, including such human pathological conditions as fibromyalgia.