| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Research Abstract |
A patch-clamp analysis was carried out using brain slices obtained from rats of 12-20 postnatal (P12-20) to elucidate the modulatory roles of dopamine (DA) in GABAergic synaptic transmission onto striatal cholinergic interneurons. Bath application of DA inhibited the GABAergic inhibitory postsynaptic currents (IPSCs) recorded in striatal cholinergic interneurons in a concentration-dependent manner. Pharmacological analysis using DA receptor agonists or antagonists suggests the involvement of D_2-like receptors. Analysis of miniature IPSCs suggests a presynaptic locus of DA's action. Furthermore, analysis using calcium channel subtype-specific blockers suggest the selective coupling between N-type calcium channels and presynaptic D_2-like receptors (Momiyama & Koga, J. Physiol. 523, 479-492, 2001). This is the first report that has identified the calcium channel subtype involved in DA-induced presynaptic modulation synaptic transmission.
A recent study has demonstrated that the contribution of N-type channels is limited only to early postnatal age in several central synapses (Iwasaki et al., J. Neurosci., 2000). Therefore, further analysis was performed in this striatal GABAergic synapse to elucidate the developmental change in the contribution of N-type channels in association with the change in DA-induced inhibition. The contribution of N-type channels gradually decreased with age until P60, but did not absolutely disappear. In parallel, D_2-like receptor-mediated presynaptic inhibitory effect also decreased, with the selective coupling to N-type channels remain unchanged (Momiyama, J. Physiol., 546, 483-490, 2003). This is the first study of developmental change in the modulation of central synaptic transmission by G-protein-coupled receptors in association with a change in the contribution a certain calcium channel subtype to transmission.
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