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首页> 外文期刊>The European Journal of Neuroscience >Modulation of AMPA currents by D2 dopamine receptors in striatal medium-sized spiny neurons: are dendrites necessary?
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Modulation of AMPA currents by D2 dopamine receptors in striatal medium-sized spiny neurons: are dendrites necessary?

机译:D2多巴胺受体对纹状体中型棘状神经元中AMPA电流的调节:树突是否必要?

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Abstract Glutamatergic afferents from the neocortex constitute the major excitatory input to striatal medium-sized spiny neurons (MSNs). Glutamate's actions on MSNs are modulated by dopamine (DA) through D1 and D2 receptor families. Although D1 modulation of glutamate responses has been well-characterized, the contribution of postsynaptic D2 receptors to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) responses has not been studied extensively. We examined DA modulation of AMPA currents using whole-cell voltage-clamp recordings of MSNs acutely dissociated and in slices. In dissociated cells, the D2 agonist quinpirole (10 micro m) produced small and inconsistent effects on AMPA currents. The magnitude of the current, as well as its modulation by quinpirole, was related to the dendritic elaboration of the dissociated cell. Thus, quinpirole altered AMPA currents only slightly when few initial dendritic segments were present. The amplitude of the current was greater and quinpirole consistently decreased this current in dissociated cells displaying at least three primary dendrites and several secondary and tertiary dendrites. Cyclothiazide, a compound that prevents AMPA receptor desensitization, greatly increased AMPA currents. In the presence of cyclothiazide, quinpirole also consistently reduced AMPA currents. Finally, in slices, AMPA current amplitude was always reduced after application of quinpirole. Sulpiride, a D2 antagonist, prevented attenuation of AMPA currents in both acutely dissociated neurons and neurons in slices. These results provide evidence that AMPA currents are attenuated by DA via activation of postsynaptic D2 receptors. In addition, they indicate that the dendrites and/or the amplitude of the current are important variables for DA modulation of AMPA currents in MSNs.
机译:摘要来自新皮层的谷氨酸能传入是构成纹状体中型棘状神经元(MSN)的主要兴奋性输入。谷氨酸对MSN的作用由多巴胺(DA)通过D1和D2受体家族调节。尽管已经很好地表征了谷氨酸应答的D1调节,但是尚未广泛研究突触后D2受体对α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)应答的贡献。我们检查了MSPA的急性解离和切片的全细胞电压钳记录的AMPA电流的DA调制。在离解的细胞中,D2激动剂喹吡罗(10微米)对AMPA电流产生小的和不一致的影响。电流的大小及其对喹吡罗的调节作用与离解细胞的树突状结构有关。因此,当几乎没有初始树突状节段存在时,喹吡罗只会稍微改变AMPA电流。在解离的细胞中,电流的振幅更大,喹吡罗持续降低该电流,显示至少三个初级树突以及几个次级和三次树突。可以防止AMPA受体脱敏的化合物Cyclothiazide大大增加了AMPA电流。在存在环噻嗪的情况下,喹吡罗还可以持续降低AMPA电流。最后,在切片中,应用喹吡罗后,AMPA电流幅度始终减小。 D2拮抗剂Sulpiride阻止了急性离解的神经元和切片神经元中AMPA电流的衰减。这些结果提供了证据,即通过突触后D2受体的激活,DA使AMPA电流减弱。另外,它们表明树突和/或电流幅度是MSN中AMPA电流的DA调制的重要变量。

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