|Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥2,600,000 (Direct Cost: ¥2,600,000)
It has not been clarify the pathphysiology of the pseudobulbar palsy induced by the basal ganglia deficiency. We pay attention to the basal ganglia-midbrain-reticular formation system as a key structure to understand this impairment. We attempt to analyze the microcircuits, neurotransmitters and receptors involved in this system.
Neuroanatomical and neurophysiological studies have suggested that a mesencephalic cholinergic region, pedunculopontine tegmental nucleus (PPN), plays a important role for maintaining the excitability of central nervous system, and for making the right rhythm of motor behaviors. Mesencephalic dopaminergic systems, which comprises the retrorubral field (RRF), the substantia nigra pars compacta (SNc), and the ventral tegmental area (VTA), are known to be involved in the higher brain functions including reward and consciousness, not only in the motor behavior.
We analyzed the synaptic inhibition from the substantia nigra pars reticulata (SNr), one of output nuclei of the basal ganglia, to the cholinergic neurons in the PPN, and to the dopaminergic neurons in the RRF, the SNc, and the VTA in rat in vitro slice preparations. Whole-cell patch-clamp recording combined with single-cell reverse transcription PCR technique was used.
The present study showed that electrical stimuli applied to the SNr induced inhibitory effects to both cholinergic and non-cholinergic neurons in the PPN. On the other hand, dopaminergic neurons in the RRF, the SNc and the VTA receive the inhibitory inputs from the SNr via both GABAA and GABAB receptors.
These findings suggest that the basal ganglia control the motor behavior and higher brain functions via midbrain. We think this idea would be important to understand the mechanism of the pseudobulbar palsy, and to develop the novel treatment for this disability. This work was performed under a Joint Research Program between National Institute for Physiological Sciences and Asahikawa Medical College.