Co-transmission of dopamine and GABA in periglomerular cells
Co-transmission of dopamine and GABA in periglomerular cells
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DOI：
10.1152/jn.00636.2007
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发表时间：
2008-03-01
影响因子：
2.5
通讯作者：
Westbrook, Gary L.
中科院分区：
文献类型：
--
作者：
Maher, Brady J.;Westbrook, Gary L.
然而，在脊椎动物和无脊椎动物系统中已经观察到速效和调节性递质的共同传输。在这里，我们描述了小鼠脑切片中的一群肾小球周围细胞（PND14-21），它们共同释放多巴胺和GABA。我们对在酪氨酸羟化酶（TH）启动子控制下表达增强绿色荧光蛋白（EGFP）的肾小球周围细胞进行全细胞记录。免疫标记证实EGFP+肾小球周围细胞合成TH和谷氨酸脱羧酶（GAD）。嗅觉受体神经元（ORN）传入输入的刺激在EGFP+细胞中引起兴奋性突触后电流（EPSCs），该细胞被可卡因抑制，阻断多巴胺的运输。这些作用被D2受体拮抗剂舒必利逆转。可卡因也增加了orn诱发的EPSCs的成对脉冲比。这些结果表明TH+肾小球周围细胞自发释放多巴胺。除多巴胺外，TH-EGFP+细胞还释放GABA。在标记细胞中短暂的去极化电压步骤引起尾电流，该尾电流被GABA a受体拮抗剂gabazine和镉完全阻断，这表明在肾小球周围细胞中存在钙依赖的自我抑制。然而，类似的电压步骤不足以引起d2受体介导的ORN终端抑制。我们的研究结果表明，TH+肾小球周围细胞直接被ORN输入激活，并释放多巴胺和GABA。我们认为，在正常生理条件下，检测多巴胺释放可能需要多个肾小球周围细胞的协同激活。
However co-transmission of fast-acting and modulatory transmitters has been observed in vertebrate and invertebrate systems. Here we describe a population of periglomerular cells in mouse brain slices (PND14-21) that co-release dopamine and GABA. We made whole cell recordings from periglomerular cells that expressed enhanced green fluorescent protein (EGFP) under the control of the tyrosine hyrdoxylase (TH) promoter. Immunolabeling confirmed that EGFP+ periglomerular cells synthesized TH as well as glutamic acid decarboxylase (GAD). Stimulation of olfactory receptor neuron (ORN) afferent input evoked excitatory postsynaptic currents (EPSCs) in EGFP+ cells that were inhibited by cocaine, which blocks dopamine transport. These effects were reversed by the D2 receptor antagonist sulpiride. Cocaine also increased the paired-pulse ratio of ORN-evoked EPSCs. These results demonstrate that TH+ periglomerular cells spontaneously release dopamine. In addition to dopamine, TH-EGFP+ cells also released GABA. Brief depolarizing voltage steps in labeled cells evoked a tail current that was completely blocked by the GABA A receptor antagonist gabazine and by cadmium, indicative of calcium-dependent self-inhibition in periglomerular cells. However, similar voltage steps were insufficient to cause D2-receptor mediated inhibition of ORN terminals. Our results indicate that TH+ periglomerular cells are directly activated by ORN input and release both dopamine and GABA. We suggest that concerted activation of multiple periglomerular cells may be required to detect dopamine release under normal physiological conditions.