Dopamine modulates release from corticostriatal terminals
Dopamine modulates release from corticostriatal terminals
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DOI：
10.1523/jneurosci.2891-04.2004
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发表时间：
2004-10-27
影响因子：
5.3
通讯作者：
Meshul, CK
中科院分区：
文献类型：
--
作者：
Bamford, NS;Robinson, S;Meshul, CK
正常纹状体功能依赖于突触多巴胺的可用性来调节神经传递。在纹状体内，皮层谷氨酸能神经元的兴奋性输入和中脑多巴胺神经元的调节性输入汇聚到中棘神经元的树突棘上。除了中棘神经元上的多巴胺受体外，D2受体也存在于皮质纹状体末端，在那里它们抑制纹状体兴奋。为了确定多巴胺缺失对皮质纹状体活动的影响，我们使用苯乙烯染料FM1-43结合多光子共聚焦显微镜对多巴胺缺乏（DD）和利血平处理的小鼠的切片制备进行了观察。FM1-43在皮质纹状体末端的活性依赖性释放允许通过荧光强度的半衰期衰减来量化动力学测量。在DD、利血平处理和对照小鼠中，暴露于d2样受体激动剂喹匹罗显示皮质纹状体动力学的调节与FM1-43染色的抑制。在DD和利血平治疗的小鼠中，喹匹罗在更大程度上降低了染色，且剂量较低，与皮质纹状体D2受体过敏一致。与对照组相比，DD小鼠的切片对安非他明或可卡因没有多巴胺释放纹状体刺激反应，除非动物预先用l -3,4-二羟基苯丙氨酸（L-dopa）处理。纹状体内谷氨酸末端的电子显微镜和免疫金标记表明，DD小鼠皮质纹状体末端动力学的差异不是由于细胞结构或谷氨酸密度的异常。微透析显示DD小鼠基底细胞外纹状体谷氨酸正常。这些数据表明多巴胺缺乏导致D2受体敏感的皮质纹状体终末形态正常。
Normal striatal function is dependent on the availability of synaptic dopamine to modulate neurotransmission. Within the striatum, excitatory inputs from cortical glutamatergic neurons and modulatory inputs from midbrain dopamine neurons converge onto dendritic spines of medium spiny neurons. In addition to dopamine receptors on medium spiny neurons, D2 receptors are also present on corticostriatal terminals, where they act to dampen striatal excitation. To determine the effect of dopamine depletion on corticostriatal activity, we used the styryl dye FM1-43 in combination with multiphoton confocal microscopy in slice preparations from dopamine-deficient (DD) and reserpine-treated mice. The activity-dependent release of FM1-43 out of corticostriatal terminals allows a measure of kinetics quantified by the halftime decay of fluorescence intensity. In DD, reserpine-treated, and control mice, exposure to the D2-like receptor agonist quinpirole revealed modulation of corticostriatal kinetics with depression of FM1-43 destaining. In DD and reserpine-treated mice, quinpirole decreased destaining to a greater extent, and at a lower dose, consistent with hypersensitive corticostriatal D2 receptors. Compared with controls, slices from DD mice did not react to amphetamine or to cocaine with dopamine-releasing striatal stimulation unless the animals were pretreated with L-3,4-dihydroxyphenylalanine (L-dopa). Electron microscopy and immunogold labeling for glutamate terminals within the striatum demonstrated that the observed differences in kinetics of corticostriatal terminals in DD mice were not attributable to aberrant cytoarchitecture or glutamate density. Microdialysis revealed that basal extracellular striatal glutamate was normal in DD mice. These data indicate that dopamine deficiency results in morphologically normal corticostriatal terminals with hypersensitive D2 receptors.