NEUROTRANSMITTER MECHANISMS IN CANINE NARCOLEPSY

这个项目的目标是确定单胺，乙酰胆碱 和其他神经递质在中枢神经系统中相互作用， 调节发作性睡病中的昏厥和嗜睡。药理 化合物被注射到特定的大脑区域， 记录睡眠模式。神经递质的释放也被测量 在cataerosis（体内透析）期间的相同区域。 在过去的颁奖期间，我们发现， 基底前脑（BF）和脑桥网状结构（PRF）是 对毒蕈碱刺激过敏， 有助于cataerosis。乙酰胆碱的释放也增加， 在自发性紧张症期间，这两个区域都表明胆碱能 系统在此行为期间处于活动状态。我们现在假设 情绪刺激导致BF中的乙酰胆碱释放。 由于超敏反应，我们假设这会诱导 广泛的胆碱能激活和REM睡眠样症状。 第二个重要发现是多巴胺能D2/D3自身受体 腹侧被盖区（VTA）的刺激产生嗜睡， 发作性睡病狗的痉挛由于VTA是一个主要的网站， 从BF向下投射，我们假设相互作用 VTA和BF之间的差异导致了过度的白天 由嗜睡症引起的嗜睡。 在下一个颁奖期间，我们将最终测试这些假设 使用相同的方法。我们还将进一步 描述肾上腺素能系统的参与，作为我们的结果， 令人惊讶的是，这些数据表明，肾上腺素能受体的作用部位 治疗紧张症的化合物可能不涉及蓝斑。 霍乱毒素免疫细胞化学技术及定位研究 胆碱能和单胺能神经元系统也将完成 来识别神经解剖学上的联系 利用这些方法，我们将建立一种神经化学物质， 神经解剖图的结构和神经递质，控制 快速眼动（REM）睡眠并产生异常表现 嗜睡症

The goal of this project is to determine how monoamines, acetylcholine and other neurotransmitters interact in the central nervous system to regulate cataplexy and sleepiness in narcolepsy. Pharmacological compounds are injected into specific brain areas while cataplexy and sleep patterns are recorded. Neurotransmitter release is also measured in the same areas during cataplexy (in vivo dialysis). In the past award period, we have found that cholinoceptive sites within the basal forebrain (BF) and the pontine reticular formation (PRF) are hypersensitive to muscarinic stimulation and that this process contributes to cataplexy. Acetylcholine release is also increased in both areas during spontaneous cataplexy demonstrating that cholinergic systems are active during this behavior. We now hypothesize that emotional stimulation results in acetylcholine release in the BF. Because of the hypersensitivity, we hypothesize that this induces widespread cholinergic activation and REM sleep-like symptoms. A second important finding is that dopaminergic D2/D3 autoreceptor stimulation in the ventral tegmental area (VTA) produced sleepiness and cataplexy in narcoleptic dogs. Since the VTA is a major site of descending projections from the BF, we hypothesize that interactions between the VTA and the BF contribute to the excessive daytime sleepiness experienced by narcolepsy. In the next award period, we will conclusively test these hypotheses using the same methodological approach. We will also further characterize the involvement of adrenergic systems as our results to date surprisingly suggest that the site of action of adrenergic compounds on cataplexy may not involve the locus coeruleus. Immunocytochemical techniques using cholera toxin and mapping studies of the cholinergic and monoaminergic neuronal systems will also be done to identify neuroanatomical connections. Using these approaches, we will establish a neurochemical and neuroanatomical map of the structures and neurotransmitters that control rapid eye movement (REM) sleep and produce the abnormal manifestations of narcolepsy.