Corticospinal tract insult alters GABAergic circuitry in the mammalian spinal cord.
Corticospinal tract insult alters GABAergic circuitry in the mammalian spinal cord.
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DOI：
10.3389/fncir.2013.00150
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发表时间：
2013
影响因子：
3.5
通讯作者：
Kaltschmidt JA
中科院分区：
文献类型：
--
作者：
Russ JB;Verina T;Comer JD;Comi AM;Kaltschmidt JA
在围产期发育期间，皮质脊髓束（CST）投射到脊髓有助于完善脊髓回路。虽然皮质脊髓输入的到来所控制的正常发育过程变得越来越清楚，但关于围产期皮质损伤如何影响脊髓回路发育的特定方面，特别是调节脊髓反射回路的抑制性微回路，知之甚少。在这项研究中，我们试图确定缺血性皮质损伤如何影响一个特征良好的群体的抑制性，GABA能中间神经元，称为GABApre神经元，它调节感觉运动反射回路中的本体感觉末梢的效率的突触属性。我们发现，假定的GABApre interneurons接收CST输入，并使用一个既定的小鼠模型围产期中风，皮质缺血性损伤的结果在减少CST密度的中间区域的脊髓，这些interneurons居住。重要的是，CST改变仅限于损伤对侧。在GABApre中间神经元的突触末梢内，我们观察到GABA合成酶谷氨酸脱羧酶（GAD 65）的65-同种型的显著上调。与CST密度降低一致，GAD 65在皮质损伤对侧脊髓升高。在其他GABA前突触标记物或接受假手术的动物中没有观察到这种效应。我们的数据揭示了围产期中风的一种新效应，涉及脊髓下行通路的结构严重缺陷，这反过来又促进了特定脊髓GABA能回路的分子改变。
During perinatal development, corticospinal tract (CST) projections into the spinal cord help refine spinal circuitry. Although the normal developmental processes that are controlled by the arrival of corticospinal input are becoming clear, little is known about how perinatal cortical damage impacts specific aspects of spinal circuit development, particularly the inhibitory microcircuitry that regulates spinal reflex circuits. In this study, we sought to determine how ischemic cortical damage impacts the synaptic attributes of a well-characterized population of inhibitory, GABAergic interneurons, called GABApre neurons, which modulates the efficiency of proprioceptive sensory terminals in the sensorimotor reflex circuit. We found that putative GABApre interneurons receive CST input and, using an established mouse model of perinatal stroke, that cortical ischemic injury results in a reduction of CST density within the intermediate region of the spinal cord, where these interneurons reside. Importantly, CST alterations were restricted to the side contralateral to the injury. Within the synaptic terminals of the GABApre interneurons, we observed a dramatic upregulation of the 65-isoform of the GABA synthetic enzyme glutamic acid decarboxylase (GAD65). In accordance with the CST density reduction, GAD65 was elevated on the side of the spinal cord contralateral to cortical injury. This effect was not seen for other GABApre synaptic markers or in animals that received sham surgery. Our data reveal a novel effect of perinatal stroke that involves severe deficits in the architecture of a descending spinal pathway, which in turn appear to promote molecular alterations in a specific spinal GABAergic circuit.
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