PHYSIOLOGY OF RAPHE MAGNUS CELLS DURING WAKE AND SLEEP

描述：(摘自申请者的摘要)延髓缝内的神经元 大脑皮层(Rm)在伤害性调制中起重要作用。RM细胞的反应 阿片类药物的毒热和止痛剂量导致了这一假说 Off细胞抑制和On细胞促进伤害性信息在 被麻醉的动物。然而，人们对rm的贡献知之甚少。 动物行为中的伤害性调制。拟议中的实验集中在 非5-羟色胺能RM细胞在非麻醉、自由活动中的生理学 老鼠。目标1中提出的实验将神经元的反应与 麻醉与非麻醉对全身吗啡的毒害作用 条件。剩下的目标将进一步加深我们对RM细胞如何 在行为正常的老鼠身上被激活。最近的实验表明， 非5-羟色胺能RM细胞具有状态依赖性放电，其模式是 与它们对有毒高温的反应有关。然而，由于只有一小部分 研究了神经元的数量，因为方案没有完成 许多细胞，我们的初步发现需要得到证实和推广。 因此，以对有毒热量的反应为特征的RM细胞将被 记录了行为自由、无拘无束的大鼠在醒着的时候循环， 慢波睡眠和矛盾睡眠状态。单位放电模式和流量 睡眠和清醒时的状态将被比较。神经元和行为 对热的反应，包括运动和心血管成分 无论是温暖的刺激还是有害的刺激，都将与刺激进行比较。 适用于不同的行为状态。同样，RM的反应 对无害的机械和听觉刺激的细胞进行测试和 与清醒、慢波睡眠或自相矛盾时使用的刺激相比 睡眠状态。由于感觉调节通常伴随着活跃的运动， RM细胞和运动对有害的热刺激的反应将是 在饮酒、进食和美容过程中进行了系统的研究。最终目标将是 测试RM细胞是否与观察到的睡眠时间的减少有关 慢性疼痛状况。首先，将连续记录RM电池的放电 在关节炎的发展过程中，会与发展中的 关节炎痛觉过敏和动物表现出的睡眠/觉醒模式。 第二，微量注射GABAA受体拮抗剂荷包牡丹碱，这是 已知激活RM OFF细胞将用于测试OFF细胞是否激活 会增加关节炎动物的睡眠时间。确定是否关闭单元格 主要作用于睡眠/觉醒调节或伤害性信息传递，其影响 荷包牡丹碱对睡眠/觉醒模式和自发性疼痛行为的影响 比较一下。

DESCRIPTION: (adapted from applicant's abstract) Neurons in the medullary raphe magnus (RM) are important in nociceptive modulation. The responses of RM cells to noxious heat and to analgesic doses of opioids have led to the hypothesis that OFF cells inhibit and ON cells facilitate nociceptive transmission in the anesthetized animal. However, little is known of how RM contributes to nociceptive modulation in behaving animals. The proposed experiments focus on the physiology of non-serotonergic RM cells in unanesthetized, freely behaving rats. The experiments proposed in Aim 1 compare the neuronal responses to noxious heat and to systemic morphine in anesthetized and unanesthetized conditions. The remaining aims will further our understanding of how RM cells are activated in behaving rats. Recent experiments suggest that non-serotonergic RM cells have state-dependent discharge in a pattern that is correlated to their response to noxious heat. However, since only a small number of neurons were studied and since the protocol was not completed for many cells, our preliminary findings need to be confirmed and extended. Therefore, RM cells, characterized by their response to noxious heat, will be recorded in freely behaving, unrestrained rats as they cycle through waking, slow wave sleep and paradoxical sleep states. Unit discharge pattern and rate during sleep and wake states will be compared. Neuronal and behavioral responses, including motor and cardiovascular components, to thermal stimulation of either warm or noxious intensity, will be compared for stimuli applied during different behavioral states. Similarly, the responses of RM cells to innocuous mechanical and auditory stimulation will be tested and compared for stimuli applied during waking, slow wave sleep or paradoxical sleep states. Since sensory modulation commonly accompanies active movements, RM cell and motor responses to noxious thermal stimulation will be systematically studied during drinking, eating and grooming. The final aim will test whether RM cells contribute to the decrease in sleep time observed during chronic pain conditions. First, RM cell discharge will be continuously recorded during the development of arthritis and will be compared to the development of arthritic hyperalgesia and to the sleep/wake pattern exhibited by the animal. Second, microinjection of the GABAA receptor antagonist, bicuculline, which is known to activate RM OFF cells will be used to test whether OFF cell activation can increase sleep time in arthritic animals. To determine whether OFF cells act primarily on sleep/wake regulation or nociceptive transmission, the effects of bicuculline on sleep/wake pattern and spontaneous pain behaviors will be compared.