CI-2 Modulation of Spinal Processes: Supraspinal Effects

描述(申请人提供)：本研究的目的是研究起源于C1-C2区域的固有脊髓通路(S)神经元如何处理来自杏仁核、蓝斑下/臂旁核(SC/PB)和迷走神经传入纤维的信息，以调节脊髓中的感觉-运动整合。我们先前证实，化学刺激C1-C2神经元可以调节腰椎脊髓神经元的自发和内脏诱发活动，以及胸椎旁肌的肌电活动。我们的初步数据进一步表明，化学刺激C1C2神经元可以强烈影响T3-T4呼吸相关中间神经元的活动。对这一应用尤为关键的是，我们的初步结果表明，鹅膏油酸对C1-C2神经元的兴奋毒性阻断，减弱了杏仁核和腰椎脊髓细胞的SC/PB调制。同样的损伤减少了对腰骶神经细胞和椎旁肌的迷走神经效应。我们的结果挑战了这样的假设，即来自棘上区域的下行通路仅通过直接投射来调节胸椎和腰椎神经元的活动。本申请提出的假设是，C1-C2神经元处理来自杏仁核、SC/PB和迷走神经传入的信息。反过来，C1-C2神经元强烈影响脊髓感觉神经元、与胸腔呼吸相关的中间神经元和躯体运动反射的活动。我们还假设杏仁核和迷走神经传入通过SC/PB核向C1-C2神经元传递信息。本文旨在回答以下问题：1)刺激特定的脊髓上核团是否会影响C1-C2神经元的放电模式和放电活动？2)C1-C2节段的神经元是否处理来自特定脊髓上核团的信息，从而改变脊髓的感觉和整合/运动活动？3)C1-C2节段的神经元是否处理来自迷走神经传入的信息，以改变脊髓的整合/运动和感觉活动？4)SC/PB核团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，以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，并使用c-fos作为神经元激活的标志。

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.