Department of Biological Sciences, Lehman College, City College, New York, NY 10468, USA.
Dev Neurosci. 2012;34(6):463-76. doi: 10.1159/000343911. Epub 2013 Feb 12.
Research suggests that the medial dorsal nucleus (MD) of the thalamus influences pyramidal cell development in the prefrontal cortex (PFC) in an activity-dependent manner. The MD is reciprocally connected to the PFC. Many psychiatric disorders, such as schizophrenia, affect the PFC, and one of the most consistent findings in schizophrenia is a decrease in volume and neuronal number in the MD. Therefore, understanding the role the MD plays in the development of the PFC is important and may help in understanding the progression of psychiatric disorders that have their root in development. Focusing on the interplay between the MD and the PFC, this study examined the hypothesis that the MD plays a role in the dendritic development of pyramidal cells in the PFC. Unilateral electrolytic lesions of the MD in Long-Evans rat pups were made on postnatal day 4 (P4), and the animals developed to P60. We then examined dendritic morphology by examining MAP2 immunostaining and by using Golgi techniques to determine basilar dendrite number and spine density. Additionally, we examined pyramidal cell density in cingulate area 1 (Cg1), prelimbic region, and dorsolateral anterior cortex, which receive afferents from the MD. Thalamic lesions caused a mean MD volume decrease of 12.4% which led to a significant decrease in MAP2 staining in both superficial and deep layers in all 3 cortical areas. The lesions also caused a significant decrease in spine density and in the number of primary and secondary basilar dendrites on superficial and deep layer pyramidal neurons in all 3 regions. No significant difference was observed in pyramidal cell density in any of the regions or layers, but a nonsignificant increase in cell density was observed in 2 regions. Our data are thus consistent with the hypothesis that the MD plays a role in the development of the PFC and, therefore, may be a good model to begin to examine neurodevelopmental disorders such as autism and schizophrenia.
研究表明，丘脑的内侧背核（MD）以活动依赖的方式影响前额叶皮层（PFC）中的锥体神经元发育。MD 与 PFC 之间存在相互联系。许多精神疾病，如精神分裂症，都会影响 PFC，而精神分裂症最一致的发现之一是 MD 中的体积和神经元数量减少。因此，了解 MD 在 PFC 发育中所起的作用很重要，这可能有助于理解以发育为根源的精神疾病的进展。本研究聚焦于 MD 和 PFC 之间的相互作用，检验了 MD 在后丘脑神经元树突发育中起作用的假设。在新生第 4 天（P4）对长耳大仓鼠幼仔的 MD 进行单侧电解损伤，动物发育至 P60。然后，我们通过 MAP2 免疫染色和使用 Golgi 技术检查基底树突数量和棘突密度来检查树突形态。此外，我们还检查了接受 MD 传入的扣带前回 1 区（Cg1）、前扣带回区和背外侧前皮质中的锥体神经元密度。丘脑损伤导致 MD 体积平均减少 12.4%，导致所有 3 个皮质区的浅层和深层 MAP2 染色均显著减少。损伤还导致所有 3 个区域的浅层和深层锥体神经元的棘突密度以及初级和次级基底树突数量显著减少。在任何区域或层中，锥体神经元密度均未观察到显著差异，但在 2 个区域观察到细胞密度略有增加。因此，我们的数据与 MD 在后脑皮质发育中起作用的假设一致，因此可能是一个很好的模型，可以开始研究自闭症和精神分裂症等神经发育障碍。
