ANESTHETIC EFFECTS ON SENSORIMOTOR INTEGRATION

最近的证据支持脊髓是麻醉剂抑制运动的部位的观点 由有害刺激引起的。虽然我们对特定神经递质的理解已经取得了进展， 受体，我们缺乏对这些麻醉作用的理解， 整合水平，例如，在脊髓的位置和类型的神经元做麻醉效果相互作用， 产生不动？为了阐明麻醉对感觉运动加工的影响，本建议 将使用神经生理学方法评估异氟烷（ISO）、氟烷（HAL）和丙泊酚的作用 （PROP）在几个脊髓部位（背角;中间角和腹角）和解剖学上或 功能不同的神经元类型（宽动态范围、伤害感受特异性神经元、感觉神经元 具有上行投射、前运动中间神经元）。在目标1中，我们将检验麻醉剂 在脊髓不同深度对神经元的影响不同。我们假设ISO将有 主要作用于腹侧脊髓部位，而HAL和PROP将对背侧和 腹侧脊髓部位。在目标2中，我们将检验具有上行投射的神经元（如 如脊髓丘脑神经元）与局部节段神经元相比对麻醉剂更敏感。 此外，在目标2中，我们将测试宽动态范围神经元更能抵抗 麻醉与伤害感受特异性神经元的比较。在目标3中，我们将检验GABA-A 拮抗作用（印防己毒素）、甘氨酸拮抗作用（士的宁）和谷氨酸激动作用（NMDA）将逆转 以麻醉特异性方式麻醉抑制脊髓神经元功能，并伴有GABA拮抗作用 对PROP和谷氨酸更特异，甘氨酸拮抗作用对ISO和HAL更特异。 结果将导致更好地了解麻醉剂如何调节神经元功能， 系统集成水平。了解麻醉剂的作用方式和作用部位将最终导致 开发更好、更安全的麻醉剂，从而降低围手术期发病率和死亡率， 改善公共卫生。

Recent evidence supports the notion that the spinal cord is the site where anesthetics suppress movement resulting from noxious stimuli. While gains have been made in our understanding of specific neurotransmitter receptors that are modulated by anesthetics, we lack understanding of these anesthetic actions at an ntegrative level, e.g., at which spinal cord locations and types of neurons do anesthetic effects interact to oroduce immobility? To shed light on anesthetic effects on sensorimotor processing, the present proposal will use neurophysiological methods to assess the effects of isoflurane (ISO), halothane (HAL) and propofol (PROP) at several spinal sites (dorsal horn; intermediate and ventral horn) and on anatomically or functionally different neuronal types (wide-dynamic range, nociceptive specific neurons, sensory neurons with ascending projections, pre-motor interneurons). In Aim 1we will test the hypothesis that anesthetics differ in their effects on neurons at different depths in the spinal cord. We hypothesize that ISO will have predominant effects at ventral spinal cord sites, whereas HAL and PROP will have effects on both dorsal and ventral spinal cord sites. In Aim 2 we will test the hypothesis that neurons with ascending projections (such as spinothalamic neurons) are more sensitive to anesthetics as compared to local segmental neurons. Furthermore, in Aim 2, we will test the hypothesis that wide-dynamic range neurons are more resistant to anesthesia compared to nociceptive specific neurons. In Aim 3, we will test the hypothesis that GABA-A antagonism (picrotoxin), glycine antagonism (strychnine) and glutamate agonism (NMDA) will reverse anesthetic depression of spinal cord neuronal function in an anesthetic-specific way, with GABA antagonism being more specific for PROP and glutamate and glycine antagonism being more specific for ISO and HAL. The results will lead to a better understanding of how anesthetics modulate neuronal function at an integrative systems level. Understanding how and where anesthetics act will eventually lead to the development of better and safer anesthetics, thereby decreasing peri-operative morbidity and mortality and improving public health.