Distinct roles of GABAergic interneurons in the regulation of striatal output pathways.
Distinct roles of GABAergic interneurons in the regulation of striatal output pathways.
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DOI：
10.1523/jneurosci.4870-09.2010
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发表时间：
2010-02-10
期刊：
影响因子：
--
通讯作者：
Kreitzer AC
中科院分区：
文献类型：
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作者：
Gittis AH;Nelson AB;Thwin MT;Palop JJ;Kreitzer AC
纹状体GABA能微电路对运动功能至关重要，但由于难以靶向纹状体中间神经元进行电生理分析，因此其性质仍然是个谜。在这里，我们利用Lhx 6-GFP转基因小鼠，以确定GABA能中间神经元，并调查其调节纹状体直接和间接途径中型棘神经元（MSN）。我们发现两个主要的中间神经元群体，持续低阈值尖峰（PLTS）和快速尖峰（FS）中间神经元，在兴奋性输入和抑制性输出方面存在显着差异。从PLTS中间神经元记录的兴奋性突触电流的特征在于小的非整流AMPA受体介导的成分和NMDA受体介导的成分。相比之下，FS中间神经元的突触能电流有一个大的，强整流AMPA受体介导的组件，但没有检测到的NMDA受体介导的反应。与其轴突形态一致，单个PLTS中间神经元的输出相对较弱且稀疏，而FS中间神经元与MSN和其他FS中间神经元牢固连接，并且似乎介导了大量前馈抑制。FS输出的突触抑制对发射频率相对不敏感，动态钳实验表明，这些短期动态使前馈抑制在很宽的频率范围内保持有效。令人惊讶的是，我们发现FS中间神经元优先靶向直接通路MSNs而不是间接通路MSNs，这表明了纹状体输出通路的快速通路特异性调节的潜在机制。
Striatal GABAergic microcircuits are critical for motor function, yet their properties remain enigmatic due to difficulties in targeting striatal interneurons for electrophysiological analysis. Here, we utilize Lhx6-GFP transgenic mice to identify GABAergic interneurons and investigate their regulation of striatal direct- and indirect-pathway medium spiny neurons (MSNs). We find that the two major interneuron populations, persistent low-threshold spiking (PLTS) and fast spiking (FS) interneurons, differ substantially in their excitatory inputs and inhibitory outputs. Excitatory synaptic currents recorded from PLTS interneurons are characterized by a small, non-rectifying AMPA receptor-mediated component and a NMDA receptor-mediated component. In contrast, glutamatergic synaptic currents in FS interneurons have a large, strongly-rectifying AMPA receptor-mediated component, but no detectable NMDA receptor-mediated responses. Consistent with their axonal morphology, the output of individual PLTS interneurons is relatively weak and sparse, whereas FS interneurons are robustly connected to MSNs and other FS interneurons and appear to mediate the bulk of feedforward inhibition. Synaptic depression of FS outputs is relatively insensitive to firing frequency, and dynamic-clamp experiments reveal that these short-term dynamics enable feedforward inhibition to remain efficacious across a broad frequency range. Surprisingly, we find that FS interneurons preferentially target direct-pathway MSNs over indirect-pathway MSNs, suggesting a potential mechanism for rapid pathway-specific regulation of striatal output pathways.