ANESTHETIC EFFECTS ON SENSORIMOTOR INTEGRATION

我们研究工作的长期目标是阐明脊髓和大脑对麻醉效果的相互作用。最近的数据表明-异氟烷在脊髓中的作用抑制了对有害刺激的运动反应。异氟烷（ISO）和氟烷（HAL），在0.6和0.9 MAC之间，降低了在最大有害刺激期间和之后发生的运动次数（对运动力的影响较小），在0.9到1.1 MAC过渡期间，减少了运动次数和运动力。然而，尚不清楚中枢神经系统中的特定部位是如何参与这些麻醉作用的。可能的脊髓和棘上部位包括背角、中枢模式产生器、前腹侧髓质（RVM）和大脑皮层的ON和off细胞。本提案的具体目的是确定1)麻醉对on /OFF细胞和背角细胞的影响（宽动态范围和伤害性特异性），以及这些影响如何与运动模式相关；2)是否失觉、背外侧索（DLF）病变和可逆的颈脊髓冷却阻滞通过消除任何下降影响来改变由最大刺激引起的运动模式；3)麻醉对中枢模式产生器的影响。我们假设1)在低而非中等ISO和HAL浓度下，ON/OFF和背角细胞活性与运动相关；2) DLF病变（通过切断RVM和脊髓背角细胞之间的通信）、脊髓冷却（可逆性脊髓化）和丘前失觉会在低ISO和HAL浓度下抑制运动模式；3)在临床相关浓度下，ISO和HAL会破坏中枢模式发生器。了解脑/脊髓与麻醉作用之间的关系将有助于阐明麻醉关键终点（对有害刺激的遗忘、无意识、不动）之间的关系，将指导对麻醉机制的进一步研究，并将导致特定部位的麻醉剂。

The long term goal of our research efforts is to elucidate the interactive contributions of the spinal cord and brain to anesthetic efficacy. Recent data suggest that -isoflurane action in the spinal cord suppresses movement responses to noxious stimuli. Isoflurane (ISO) and halothane (HAL), between 0.6 and 0.9 MAC, depress the number of movements (with less effect on the force of the movements) that occur during and after supramaximal noxious stimulation, and at the 0.9 to 1.1 MAC transition, decrease the number of movements and the force of the movements. It is unclear, however, how specific sites within the central nervous system participate in these anesthetic effects. Possible spinal and supraspinal sites include the dorsal horn, central pattern generators, ON- and OFF-cells of the rostralventral medulla (RVM) and cerebral cortex. The specific aims of this proposal are to determine 1) anesthetic effects on ON/OFF cells and dorsal horn cells (wide dynamic-range and nociceptive specific), and how these effects correlate with the movement pattern; 2) whether decerebration, dorsolateral funiculus (DLF) lesions and reversible cooling block of the cervical spinal cord alters the movement pattern arising from supramaximal stimulation by eliminating any descending influences; 3) anesthetic effects on central pattern generators. We hypothesize that 1) ON/OFF and dorsal horn cell activity is correlated with movement at low but not moderate ISO and HAL concentrations; 2) DLF lesions (by severing communication between the RVM and spinal dorsal horn cells), spinal cord cooling (reversible spinalization) and pre-collicular decerebration will depress the movement pattern at low ISO and HAL concentrations; 3) ISO and HAL will disrupt central pattern generators at clinically relevant concentrations. Understanding the brain/spinal cord relationship vis-a-vis anesthetic action will aid elucidation of the relationship among critical end-points of anesthesia (amnesia, unconsciousness, immobility in response to noxious stimulation), will guide further research into anesthetic mechanisms, and will lead to site-specific anesthetics.