The purpose of this study is to examine how neurons of propriospinal pathway(s) originating in the C1-C2 region process information from amygdala, subcoeruleus/parabrachial (SC/PB) nuclei, and vagal afferent fibers to modulate sensory-motor integration in the spinal cord. We previously demonstrated that chemical stimulation of C1-C2 neurons modulated spontaneous and visceral-evoked activity in lumbosacral spinal neurons and EMG activity of thoracic paraspinal muscles. Our preliminary data further demonstrate that chemical stimulation of C1 C2 neurons can strongly influence the activity of T3-T4 respiratory-related interneurons. Especially critical to this application are our preliminary results indicating that excitotoxic blockade of C1-C2 neurons with ibotenic acid, attenuated amygdalar and SC/PB modulation of lumbosacral spinal cells. The same lesion reduced vagal effects on lumbosacral neurons and paraspinal muscles. Our results challenge the assumption that descending pathways from supraspinal regions modulate activity of thoracic and lumbosacral neurons through direct projections only. The present application addresses the hypothesis that C1-C2 neurons process information from amygdala, SC/PB and vagal afferents. In turn, C1-C2 neurons strongly influence activity of spinal sensory neurons, thoracic respiration-related interneurons, and somatomotor reflexes. We also hypothesize that amygdala and vagal afferents transmit information to C1-C2 neurons via SC/PB nuclei.
Specific aims are designed to answer the following questions: 1) Are discharge patterns and activities of C1-C2 neurons affected by stimulating specific supraspinal nuclei? 2) Do neurons in C1-C2 segments process information from specific supraspinal nuclei to change sensory and integrative/motor activity in the spinal cord? 3) Do neurons in C1-C2 segments process information from vagal afferents to change integrative/motor and sensory activity in the spinal cord? 4) Do SC/PB nuclei relay information from amygdala and vagal afferent fibers to the C1-C2 segments to change sensory and integrative/motor activity in the spinal cord? Neurophysiological studies to examine extracellular discharge patterns and studies using c-fos as a marker of neuronal activation will be conducted in anesthetized rats.
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