Invivoパッチクランプ法を用いた線条体シナプス伝達機構の解析

点击翻译按钮获取中文摘要

Whole-cell patch-clamp recordings were carried out from neurons in the striatum and basal forebrain nuclei (BF). Membrane properties and profiles of synaptic transmission as well as its modulation were analyzed in various types of neurons.I) Cholinergic neurons in the rat BF were morphologically identified with the antibody for the receptor of a neurotrophic factor. This method enabled the real time identification of cholinergic neurons under the fluorescent microscope in the patch-clamp experiment, enhancing the efficiency of the experiments.1) Non-NMDA glutamatergic excitatory postsynaptic currents (EPSCs) and GABAergic inhibitory postsynaptic currents (IPSCs) were recorded in BF cholinergic neurons and modulation of these EPSCs and IPSCs by somatostatin was analyzed. The study has clarified that EPSCs and IPSCs were presynaptically inhibited by activation of different sst receptors (Momiyama ＆ Zaborszky, 2006).2) The mechanisms underlying dopamine-receptor-mediated inhibition of the EPSCs evoked in BF cholinergic neurons were analyzed. The study has shown that selective coupling between dopamine D1-like receptors and P/Q-type calcium channels for glutamate release (Momiyama ＆ Fukazawa, 2007).II) Analyses using dopamine receptor knock out mice have revealed that dopamine D2-like receptors are involved in the frequently-dependent suppression of GABA release onto cholinergic interneurons in the striatum (Momiyama ＆ Fukazawa, 2007).III) Abnormal behaviors were ameliorated in the Parkinson's disease model rats by grafting neuroepithelial stem cells of rats or swine, and morphological and electrophysiological studies have demonstrated that grafted cells survived in the host striatum to differentiate into functionally active neurons (in preparation).