| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Research Abstract |
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
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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). Then
These 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
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