CI-2 Modulation of Spinal Processes: Supraspinal Effects

描述（由申请人提供）：本研究的目的是检查起源于C1-C2区域的脊髓本体通路神经元如何处理来自杏仁核、蓝斑下/臂旁（SC/PB）核和迷走传入纤维的信息，以调节脊髓中的感觉-运动整合。我们以前证明，C1-C2神经元的化学刺激调制自发和内脏诱发的活动，腰骶脊髓神经元和肌电图活动的胸椎旁肌。我们的初步数据进一步表明，C1-C2神经元的化学刺激可以强烈影响T3-T4神经元相关的中间神经元的活动。特别重要的是，我们的初步结果表明，C1-C2神经元与鹅膏蕈氨酸，衰减杏仁和SC/PB调制腰骶脊髓细胞的兴奋性毒性封锁。同样的损伤减少迷走神经对腰骶神经元和椎旁肌的影响。我们的研究结果挑战的假设，从脊髓上区域的下行通路调节胸和腰骶神经元的活动，通过直接投射。本申请解决了C1-C2神经元处理来自杏仁核、SC/PB和迷走神经传入的信息的假设。反过来，C1-C2神经元强烈影响脊髓感觉神经元、胸呼吸相关中间神经元和躯体运动反射的活动。我们还推测杏仁核和迷走神经传入通过SC/PB核将信息传递到C1-C2神经元。本研究旨在回答以下问题：1）刺激特定的脊髓上核是否会影响C1-C2神经元的放电模式和活动？2)C1-C2节段的神经元处理来自特定脊髓上核的信息以改变脊髓的感觉和整合/运动活动吗？3)C1-C2节段的神经元处理迷走神经传入的信息以改变脊髓中的整合/运动和感觉活动吗？4)SC/PB核是否将杏仁核和迷走神经传入纤维的信息传递到C1-C2节段，从而改变脊髓的感觉和整合/运动活动？将在麻醉大鼠中进行神经生理学研究以检查细胞外放电模式和使用c-fos作为神经元活化标志物的研究。

DESCRIPTION (provided by applicant): 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.