Analysis of function of dopamine as a retrograde messenger in the basal ganglia

多巴胺作为基底节逆行信使的功能分析

• 批准号: 15500292
• 负责人: MOMIYAMA Toshihiko
• 金额: $ 2.11万
• 依托单位: National Institute for Physiological Sciences (2004)Okazaki National Research Institutes (2003)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15500292/
• 关键词: dopamine; depolarization; glutamate; slice; retrograde messenger; D2-lioke receptor; basal ganglia; patch-clamp; 腹側被蓋野; 興奮性シナプス; D2型受容型; ノックアウトマウス; 抗体; 興奮性シナプス後電流; D_2型受容体; 抑制

Whole-cell patch-clamp study was carried out to elucidate physiological roles of dopamine (DA) using midbrain slices of the mice (P13-21). EPSCs mediated by non-NMDA glutamate receptors were evoked in the ventral tegmental dopaminergic neurons by focal stimulation at the holding potential of -60 mV. Application of a depolarizing pulse to 0 mV for 5 s inhibited the EPSCs by 42.8 ± 3.1% (n=16) in wild type mice. The magnitude of depolarization-induced inhibition of EPSCs (DSE) was significantly (P<0.05) reduced to 7.3 ± 9.9% (n=5) in the presence of a D2-like receptor antagonist, sulpiride (5 μM), in the bathing solution. DSE amplitude was also significantly (P<0.05) small in slices obtained from D2 receptor deficient mice (7.3 ± 2.0%, n=17). DSE was also observed by action potential generation induced by depolarizing pulses in the current-clamp mode (36.5 ± 5.9%, n=5). These results suggest that DA released from dopaminergic neurons acts on presynaptic D2 receptors to inhibit glutamate release, implying a role of DA as a retrograde messenger in the central nervous system.

采用全细胞膜片钳技术研究多巴胺（DA）在小鼠中脑（P13-21）的生理作用。在保持电位为-60 mV时，局灶性刺激腹侧被盖多巴胺能神经元可诱发由非NMDA谷氨酸受体介导的EPSC。在野生型小鼠中，施加去极化脉冲至0 mV持续5s抑制EPSC 42.8 ± 3.1%（n=16）。在5 μM的D2样受体拮抗剂舒必利存在下，去极化诱导的EPSCs抑制幅度（DSE）显著降低（P<0.05）至7.3 ± 9.9%（n=5）。D2受体缺陷小鼠脑片的DSE振幅也显著（P<0.05）小（7.3 ± 2.0%，n=17）。在电流钳模式下，通过去极化脉冲诱导的动作电位产生也观察到DSE（36.5 ± 5.9%，n=5）。这些结果表明，多巴胺能神经元释放的DA作用于突触前D2受体，以抑制谷氨酸的释放，这意味着DA在中枢神经系统中作为一个逆行信使的作用。

项目成果

Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in DAP12-deficient mice

• DOI: 10.1172/jci200316923
• 发表时间: 2003-02-01
• 期刊: JOURNAL OF CLINICAL INVESTIGATION
• 影响因子: 15.9
• 作者: Kaifu, T;Nakahara, J;Takai, T
• 通讯作者: Takai, T

スライスパッチクランプ法を用いた中枢シナプス伝達機構の解析

切片膜片钳法分析中枢突触传递机制

• 发表时间: 2003
• 期刊: 日本薬理学雑誌 121.3
• 作者: Momiyama;T.;Kaifu T. et al.;籾山俊彦
• 通讯作者: 籾山俊彦

Potential functional neural repair with grafted neural stem cells of early embryonic neuroepithelial origin.

早期胚胎神经上皮来源的移植神经干细胞的潜在功能性神经修复。

• 发表时间: 2005
• 期刊: Neuroscience Research (in press)
• 作者: Uchida;K.;Momiyama;T.;Okano;H.;Yuzaki;M.;Koizumi;A.;Mine;Y;Kawase;T.
• 通讯作者: T.

Parallel decrease in ω-conotoxin-sensitive transmission and dopamine-induced inhibition at the striatal synapse of development rats

发育中大鼠纹状体突触中 ω-芋螺毒素敏感传递和多巴胺诱导的抑制平行减少

• 发表时间: 2003
• 期刊: Journal of Physiology 546(2)
• 作者: Oshio K;Chiba A;Inase M;Toshihiko Momiyama
• 通讯作者: Toshihiko Momiyama

Parallel decrease in ω-conotoxin-sensitive transmission and dopamine-induced inhibition at the striatal synapse of developing rats.

发育中大鼠纹状体突触的 ω-芋螺毒素敏感传递和多巴胺诱导的抑制同时减少。

• 发表时间: 2003
• 期刊: Journal of Physiology 546(2)
• 作者: Momiyama;T.
• 通讯作者: T.