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Spatial and Temporal Bias in the Mitotic Origins of Somatostatin- and Parvalbumin-Expressing Interneuron Subgroups and the Chandelier Subtype in the Medial Ganglionic Eminence

机译:表达生长抑素和小白蛋白的中间神经元亚群和内侧神经节隆起的枝形吊灯亚型的有丝分裂起源的时空偏向

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摘要

GABAergic interneurons modulate cortical activity through the actions of distinct subgroups. Recent studies using interneuron transplants have shown tremendous promise as cell-based therapies for seizure disorders, Parkinson’s disease, and in the study of neocortical plasticity. Previous reports identified a spatial bias for the origins of parvalbumin (PV)- and somatostatin (SST)-expressing interneuron subgroups within the medial ganglionic eminence (MGE). In the current study, the mitotic origins of these interneurons are examined by harvesting MGE cells at 2 time points and evaluating their neurochemical profiles after transplantation into neonatal mouse cortex. Although the dorsal MGE (dMGE)-SST and ventral MGE (vMGE)-PV bias were confirmed, both subgroups originate from progenitors located throughout the MGE. The dMGE bias was also found for SST subgroups that coexpress calretinin or reelin. In contrast, another major subgroup of SST interneuron, neuropeptide Y-expressing, does not appear to originate within the MGE. Finally, novel evidence is provided that a clinically important subtype of PV-expressing interneuron, the chandelier (axo-axonic) cell, is greatly enriched in transplants from the vMGE at embryonic day 15. These findings have important implications both for the study of interneuron fate determination and for studies that use interneuron precursor transplantation to alter cortical activity.
机译:GABA能中神经元通过不同亚组的作用来调节皮层活动。最近使用神经元间移植的研究表明,作为治疗癫痫,帕金森氏病和新皮层可塑性的细胞疗法具有广阔的前景。先前的报告确定了内侧神经节隆起(MGE)中表达小白蛋白(PV)和生长抑素(SST)的中间神经元亚群的空间偏倚。在当前的研究中,通过在两个时间点采集MGE细胞并评估它们移植到新生小鼠皮层后的神经化学特征,来检查这些中间神经元的有丝分裂起源。尽管证实了背侧MGE(dMGE)-SST和腹侧MGE(vMGE)-PV偏倚,但这两个亚组均来自整个MGE的祖细胞。还发现共表达钙调蛋白或reelin的SST亚组的dMGE偏倚。相反,SST中间神经元的另一个主要亚群,即表达神经肽Y,似乎并不起源于MGE内。最后,提供了新的证据表明,在胚胎第15天时,表达vPV的中间神经元的临床重要亚型,即枝形吊灯(axo-axonic)细胞大大丰富了来自vMGE的移植。这些发现对中间神经元的研究均具有重要意义。命运确定以及使用中间神经元前体移植改变皮层活动的研究。

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