Differential tonic GABA conductances in striatal medium spiny neurons
Differential tonic GABA conductances in striatal medium spiny neurons
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DOI：
10.1523/jneurosci.3908-07.2008
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发表时间：
2008-01-30
影响因子：
5.3
通讯作者：
Vicini, Stefano
中科院分区：
文献类型：
--
作者：
Ade, Kristen K.;Janssen, Megan J.;Vicini, Stefano
中棘神经元(MSN)为背侧纹状体提供主要输出。那些表达多巴胺D-2受体(D-2(+))的人投射到苍白球外部，被认为是抑制运动，而那些表达多巴胺D-1受体(D-1(+))的人投射到黑质网状部，被认为促进运动。细菌人工染色体转基因小鼠切片的全细胞和向外斑片记录研究了GABA(A)受体介导的电流在多巴胺受体D-1(+)纹状体和D-2(+)纹状体黑质MSN中的作用。尽管两个神经元群体之间的抑制性突触电流相似，但D-2(+)MSN显示出更大的GABA(A)受体介导的紧张性电流。用TTX阻断紧张性电流的程度与使用GABAA拮抗剂的程度相似，表明周围的GABA是突触起源的。与D-1(+)MSN相比，低浓度GABA在D-2(+)MSN中产生更大的全细胞反应和更长的GABA通道开放时间。来自α1(-/-)小鼠MSN的记录和紧张性电流的药理学分析表明，D-2(+)中含有α5的GABA(A)受体的表达高于D-1(+)MSN。由于帕金森氏病、亨廷顿舞蹈症和迟发性运动障碍等多种疾病是由这两条通路之间的失衡引起的，负责D-2(+)MSN紧张性电流的GABA(A)受体可能是治疗干预的潜在靶点。
Medium spiny neurons (MSNs) provide the principal output for the dorsal striatum. Those that express dopamine D-2 receptors (D-2(+)) project to the globus pallidus external and are thought to inhibit movement, whereas those that express dopamine D-1 receptors (D-1(+)) project to the substantia nigra pars reticulata and are thought to facilitate movement. Whole-cell and outside-out patch recordings in slices from bacterial artificial chromosome transgenic mice examined the role of GABA(A) receptor-mediated currents in dopamine receptor D-1(+) striatonigral and D-2(+) striatopallidal MSNs. Although inhibitory synaptic currents were similar between the two neuronal populations, D-2(+) MSNs showed greater GABA(A) receptor-mediated tonic currents. TTX application abolished the tonic current to a similar extent as GABAA antagonists, suggesting a synaptic origin of the ambient GABA. Low GABA concentrations produced larger whole-cell responses and longer GABA channel openings in D-2(+) than in D-1(+) MSNs. Recordings from MSNs in alpha 1(-/-) mice and pharmacological analysis of tonic currents suggested greater expression of alpha 5-containing GABA(A) receptors in D-2(+) than in D-1(+) MSNs. As a number of disorders such as Parkinson's disease, Huntington's chorea, and tardive dyskinesia arise from an imbalance between these two pathways, the GABA(A) receptors responsible for tonic currents in D-2(+) MSNs may be a potential target for therapeutic intervention.