|Budget Amount *help
¥7,600,000 (Direct Cost : ¥7,600,000)
Fiscal Year 1997 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1996 : ¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1995 : ¥5,000,000 (Direct Cost : ¥5,000,000)
The aim of this research project was to elucidate the physiological functions of the striatal neural circuits, focusing especially on the large aspiny neurons (cholinergic interneurons), which have been demonstrated by us to show the plastic changes during motor learning. 1, The first question was what the striato nigral and striatopallidal projection neurons (the medium spiny neurons) do on the cholinergic interneurons. I found that (1) among 4 types of striatal neurons, the cholinergic inter neurons and the somatostatinergic inter neurons showed slow depolarization or an inward current by substance P (SP), which are considered to be released from the striatonigral neurons ; (2), intrastriatal electrical stimulation induced a slow inward current, which was blocked by an antagonist of SP receptors ; (3) the effect of enkephalin on the cholinergic interneurons was to hyper polarize the membrane potential via d-opioid receptor activation, (4) It is therefore speculated that activation of
the striatonigral pathway would activate and the striatopallidal pathway would inactivate the cholinergic interneurons, which may open and close the gate for the cortico-and/or thalamostriatal pathway, respectively. 2, The second question was what dopaminereleased from the substantia nigra pars compactado on the striatal cholinergic interneurons. Our data indicated that, (1) dopamine depolarizes the striatal choliner gic cells by a D_1-like dopamine receptor-mediated suppression of resting K^+ conductance and an opening of a non-selective cation channel, and, (2) both mechanisms are mediated by an adenylyl cyclase-dependent pathway. (3) It is therefor esuggested that dopamine would directly facilitate the firing evoked by EPSPs by the thalamostriatal and corticostriatal pathways.
In conclusion, direct dopaminergic regulation of the striatal cholinergic interneurons would switch on or off the activities of the striatal projection neurons by the known muscarinic modulation of A-channels, and both pathways of the projection neurons return their outputs and regulate reciprocally the activity of the cholinergic interneurons. Less