Enkephalin Disinhibits Mu Opioid Receptor-Rich Striatal Patches via Delta Opioid Receptors.
Enkephalin Disinhibits Mu Opioid Receptor-Rich Striatal Patches via Delta Opioid Receptors.
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DOI：
10.1016/j.neuron.2015.11.010
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发表时间：
2015-12-16
期刊：
影响因子：
16.2
通讯作者：
Sabatini BL
中科院分区：
文献类型：
--
作者：
Banghart MR;Neufeld SQ;Wong NC;Sabatini BL
阿片类神经肽及其受体是进化上保守的神经调节系统，深刻地影响行为。在表达内源性阿片样脑啡肽的背侧纹状体中，斑块（或纹状体）是富含μ阿片样受体的边缘相关亚室。背侧纹状体中阿片样物质信号传导的功能意义和脑啡肽调节的斑片中的回路元件尚不清楚。在这里，我们研究了补丁输出是如何调制脑啡肽，并确定了潜在的电路机制。我们发现，补丁是相对缺乏的小白蛋白表达的中间神经元，并存在自包含的抑制性微电路。脑啡肽抑制抑制纹状体投射神经元选择性地在补丁，从而解除其发射响应皮质输入。这种神经调节的大部分是由δ，而不是μ阿片受体介导的，特异性作用于纹状体内侧支轴突的纹状体体神经元。这些结果表明，脑啡肽门在背侧纹状体边缘系统的信息流，通过特定的功能，δ阿片受体的补丁。
Opioid neuropeptides and their receptors are evolutionarily conserved neuromodulatory systems that profoundly influence behavior. In dorsal striatum, which expresses the endogenous opioid enkephalin, patches (or striosomes) are limbic-associated subcompartments enriched in mu opioid receptors. The functional implications of opioid signaling in dorsal striatum and the circuit elements in patches regulated by enkephalin are unclear. Here, we examined how patch output is modulated by enkephalin and identified the underlying circuit mechanisms. We found that patches are relatively devoid of parvalbumin-expressing interneurons and exist as self-contained inhibitory microcircuits. Enkephalin suppresses inhibition onto striatal projection neurons selectively in patches, thereby disinhibiting their firing in response to cortical input. The majority of this neuromodulation is mediated by delta, not mu opioid receptors, acting specifically on intra-striatal collateral axons of striatopallidal neurons. These results suggest that enkephalin gates limbic information flow in dorsal striatum, acting via a patch-specific function for delta opioid receptors.