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Neumbiological basis of the basal ganglia control of sleep

基底神经节控制睡眠的神经生物学基础

基本信息

批准号：
15500279
负责人：
TAKAKUSAKI Kaoru
金额：
$ 2.11万
依托单位：
Asahikawa Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15500279/
关键词：
Basal ganglia Cholinergic projections Rapid eye movement sleep postsynaptic inhibition α-motor neuron GABAergic projections Reticular formation Muscle tone アセチルコリン系 GABA作動系筋緊張レム睡眠時異常行動症候群パーキンソン病

项目摘要

The present study was designed to elucidate how the basal ganglia control sleep states via projection from the substantia nigra pars reticulata (SNr), one of the basal ganglia output nuclei, to the pedunculopontine tegmental nucleus (PPN) in the mesopontine tegmentum. For this purpose we used acute de cerebrate cats in which the striatum, thalamus, and cerebral cortex were removed, but the SNr was preserved. We have shown that repetitive electrical stimulation (10-40 μA, 50 Hz) applied to the PPN resulted in the generation of rapid eye movements (REM) which were associated with muscular atonia (REM with atonia).First we tried to elucidate synaptic mechanisms acting on motoneurons during muscular atonia induced by PPN stimulation. Intracellular recording was performed from 72 hindlimb motoneurons innervating extensor and flexor muscles, and the changes in excitability of the motoneurons following the PPN stimulation were examined. Repetitive electrical stimulation (20-50 μA, 50 Hz, 5-10 … More s) of the PPN hyperpolarized the membrane potentials of both the extensor and flexor motoneurons by 2.0-12 mV (6.0±2.3 mV, n=72). The membrane hyperpolarization persisted for 10-20 seconds even after termination of the stimulation. During the PPN stimulation, the membrane hyperpolarization was associated with decreases in the firing capability (n=28) and input resistance (28.5±6.7%, n=14) of the motoneurons. Moreover the amplitude of Ia EPSPs was also reduced (44.1±13.4 %, n=14). After the PPN stimulation, these parameters immediately returned despite that the membrane hyperpolarization persisted. Iontophoretic injections of chloride ions into the motoneurons reversed the polarity of the membrane hyperpolarization during the PPN stimulation. The polarity of the outlasting hyperpolarization however was not reversed. Next we examined how the GABAergic SNr-PPN projection regulated the PPN-induced REM with atonia. Electrical stimulation applied to the SNr blocked the PPN-induced REM with atonia, and the optimal stimulus sites for these effects were intermingled within the lateral part of the SNr. Moreover the PPN-induced REM with atonia was abolished by an injection into the PPN of muscimol (1.15 mM, 0.1-0.25 μl), a γ-amino butyric acid (GABA)_A receptor agonist, but not altered by an injection of baclofen (1-10 mM, 0.1-0.25μl), a GABA_B receptor agonist. Moreover, an injection of bicuculline (1-15 mM, 0.1-0.25 μl), a GABA_A receptor antagonist, into the PPN, resulted in REM with atonia. On the other hand, an injection of muscimol into the dorsolateral part of the SNr (1.15 mM, 0.1-0.25 μl) induced REM with atonia, which was in turn eliminated by a further injection of muscimol into the PPN (5-10 mM, 0.2-0.25 μl). ThenThese findings suggest that a postsynaptic inhibitory mechanism, which was mediated by chloride ions, was acting on hindlimb motoneurons during PPN-induced postural atonia. A GABAergic projection from the SNr to the PPN could be involved in the control of REM with atonia, signs which indicate REM sleep. An excessive GABAergic output from the basal ganglia to the PPN in parkinsonian patients may induce sleep disturbances, including a reduction of REM sleep periods. Less

本研究旨在阐明基底神经节如何通过黑质网状部（SNr）（基底神经节的输出核团之一）投射到脑桥中脑被盖的脚桥被盖核（PPN）来控制睡眠状态。为此，我们使用了急性去脑猫，其中纹状体，丘脑和大脑皮层被删除，但SNr被保留。我们发现，重复电刺激（10-40 μA，50 Hz）PPN可引起快速眼动（rapid eye movements，REM），并伴有肌张力减退（muscle atonia，REM with atonia）。对72个支配后肢伸肌和屈肌的运动神经元进行了细胞内记录，并观察了刺激PPN后运动神经元兴奋性的变化。重复电刺激（20-50 μA，50 Hz，5-10 ...更多信息 PPN使伸肌和屈肌运动神经元的膜电位超极化2.0-12 mV（6.0±2.3 mV，n=72）。即使在刺激终止后，膜超极化仍持续10-20秒。在PPN刺激过程中，膜超极化与运动神经元放电能力（n=28）和输入电阻（28.5± 6.7%，n=14）的降低有关。Ia型EPSP的波幅也降低（44.1± 13.4%，n=14）。在PPN刺激后，这些参数立即恢复，尽管膜超极化持续存在。将氯离子注入运动神经元，可逆转PPN刺激过程中膜超极化的极性。然而，超极化的极性并没有逆转。接下来，我们研究了GABA能SNr-PPN投射如何调节PPN诱导的具有张力减退的REM。对SNr施加电刺激可以阻止PPN诱导的REM伴张力不足，并且这些效应的最佳刺激部位混合在SNr的外侧部分内。向PPN内注射γ-氨基丁酸（GABA）_A受体激动剂蝇蕈醇（mussimol，1.15 mM，0.1-0.25 μl）可消除PPN诱导的REM，而注射GABA_B受体激动剂巴氯芬（baclofen，1-10 mM，0.1-0.25μl）则不改变PPN诱导的REM。此外，在PPN内注射GABA_A受体拮抗剂荷包牡丹碱（1-15 mM，0.1-0.25 μl），可引起REM伴张力减退。另一方面，将蝇蕈醇（1.15 mM，0.1-0.25 μl）注射到SNr的背外侧部分中诱导了具有张力不足的REM，而这反过来又被进一步将蝇蕈醇（5-10 mM，0.2-0.25 μl）注射到PPN中所消除。这些结果表明，在PPN诱导的姿势性肌张力减退过程中，氯离子介导的突触后抑制机制作用于后肢运动神经元。从SNr到PPN的GABA能投射可能参与了对REM的控制，并伴有张力减退，这是REM睡眠的标志。在帕金森病患者中，从基底神经节到PPN的过量GABA能输出可诱发睡眠障碍，包括REM睡眠期的减少。少

项目成果

期刊论文数量（88）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Basal ganglia efferents to the brainstem centers controlling postural muscle tone and locomotion: A new concept for understanding motor disorders in basal ganglia dysfunction

DOI：
10.1016/s0306-4522(03)00095-2
发表时间：
2003-01-01
期刊：
NEUROSCIENCE
影响因子：
3.3
作者：
Takakusaki, K;Habaguchi, T;Sakamoto, T
通讯作者：
Sakamoto, T

A selective orexin-1 receptor antagonist, SB334867, blocks 2-DG-induced gastric acid secretion in rats

DOI：
10.1016/j.neulet.2004.11.043
发表时间：
2005-03
期刊：
Neuroscience Letters
影响因子：
2.5
作者：
Hiroto Yamada;N. Takahashi;S. Tanno;Miho Nagamine;K. Takakusaki;T. Okumura
通讯作者：
Hiroto Yamada;N. Takahashi;S. Tanno;Miho Nagamine;K. Takakusaki;T. Okumura

Medullary reticulospinal tract mediating a generalized motor inhibition in cats: III. Functional organization of spinal interneurons in the lower lumbar segments

髓质网状脊髓束介导猫的全身运动抑制：III。