NEUROPHYSIOLOGICAL STUDIES OF VOMITING

恶心和呕吐(呕吐)通常与癌症有关 化疗和放射治疗、术后康复、运动和空间 疾病、怀孕和包括艾滋病在内的各种疾病。长期的 这个项目的目标是确定产生 在各种情况下呕吐。加深了对神经的了解 参与的电路，以及对神经递质的日益增长的知识 受体亚型，应该导致改进的药物 对策。研究将使用“虚构的呕吐”进行。 实验模型，它的特征是一系列的 大鼠膈(膈)神经和腹部运动神经的共同激活 去大脑、瘫痪的猫。具体目标是调查 触发或抑制呕吐的神经输入和中枢神经元 产生呕吐的电路，包括参与的运动前神经元 在产生呼吸肌激活模式时，呼吸肌激活对 呕吐的运动动作。 胃迷走神经、肝迷走神经和内脏神经传入的可能性 将确定触发呕吐，以及可能的交互作用 迷走神经和内脏传入与脑区重要性之间的关系 迷走神经诱发呕吐的后遗症。初步研究 提示孤束延髓核(NTS)可能发挥作用 作为不同排泄物输入的整合部位的重要角色。NTS 将对神经元进行测试，以确定它们是否收到会聚的兴奋 来自能够触发呕吐的不同输入，包括该区域 后化学感受器呕吐触发区和腹部迷走神经和 前庭神经，以及对各种催吐药物的反应 作为癌症化疗药物顺铂。呕吐是由一种 大范围的输入可以被未知的传入所抑制 颈迷走神经。这种抑制输入的来源将是 就像它的止吐作用可能是 通过抑制汇聚兴奋的NTS神经元介导的 呕吐输入。 腹部和肋间内侧呼气运动神经元接受中枢 球脊髓运动前呼气神经元的呼吸驱动 尾侧腹侧呼吸组(VRG)。呕吐时，尾部 VRG呼气神经元有两种不同的放电模式，它们是 适合驱动腹部和肋间内侧运动神经元 呕吐时火势不同。细胞内 尾侧VRG呼气神经元的记录将确定 时相抑制产生了这两种放电模式。在……里面 此外，将进行VRG神经元的搜索，以提供 对膈神经和协同活动的兴奋性驱动的来源尚不清楚 呕吐时外肋间运动神经元。最后，一项研究将 应为控制上呼吸道作出贡献 由疑核后核神经元投射引起的呕吐 至疑核的尾侧VRG)，其中含有运动神经元 支配上呼吸道肌肉。

Nausea and vomiting (emesis) commonly occur in association with cancer chemo- and radiation therapy, post-operative recovery, motion and space sickness, pregnancy, and various diseases including AIDS. The long-term goal of this project is to determine the neural mechanisms that produce vomiting under various conditions. Increased understanding of the neural circuitry involved, together with a growing knowledge of neurotransmitter receptor subtypes, should lead to improved pharmaceutical countermeasures. Studies will be conducted using the "fictive vomiting" experimental model, which is characterized by a series of bursts of coactivation of diaphragmatic (phrenic) and abdominal motor nerves in decerebrate, paralyzed cats. The specific objectives are to investigate neural inputs that trigger or inhibit vomiting and the central neuronal circuitry that produces vomiting, including pre-motor neurons involved in generating the pattern of respiratory muscle activation critical for the motor act of vomiting. The potential for gastric vagal, hepatic vagal, and splanchnic inputs to trigger vomiting will be determined, as will possible interactions between vagal and splanchnic inputs and the importance of the area postrema in mediating vagal-induced vomiting. Preliminary studies indicate that the medullary nucleus of the solitary tract (NTS) may play an important role as an integrating site for different emetic inputs. NTS neurons will be tested to determine if they receive convergent excitation from different inputs capable of triggering vomiting, including the area postrema chemoreceptor emetic trigger zone and abdominal vagus and vestibular nerves, as well as in response to various emetic drugs such as the cancer chemotherapeutic agent cisplatin. Vomiting elicited by a broad range of inputs can be inhibited by unknown afferents in the cervical vagus nerve. The source of this inhibitory input will be determined, as will the possibility that its anti-emetic effects are mediated by inhibition of NTS neurons that are excited by convergent emetic inputs. Abdominal and internal intercostal expiratory motoneurons receive central respiratory drive from bulbospinal pre-motor expiratory neurons located in the caudal ventral respiratory group (VRG). During vomiting, caudal VRG expiratory neurons fire in two distinct patterns, which are appropriate to drive abdominal and internal intercostal motoneurons that fire out of phase with each other during vomiting. Intracellular recordings from caudal VRG expiratory neurons will determine the role of phasic inhibitory puts in producing these two discharge patterns. In addition, a search will be conducted for VRG neurons that may provide the still unknown source of excitatory drive to phrenic and co-active external intercostal motoneurons during vomiting. Finally, a study will be made of the contribution to the control of the upper airway during vomiting by a projection from neurons in the nucleus retroambigualis (in the caudal VRG) to the nucleus ambiguous, which contains motoneurons innervating upper airway musculature.