Kharazia V N, Jacobs K M, Prince D A
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University, 300 Pasteur Drive, M016, Stanford, CA 94305, USA.
Neuroscience. 2003;120(1):207-18. doi: 10.1016/s0306-4522(03)00282-3.
Rat neocortex that has been injured on the first or second postnatal day (P0-1) develops an epileptogenic, aberrantly layered malformation called a microgyrus. To investigate the effects of this developmental plasticity on inhibitory interneurons, we studied a sub-population of GABAergic cells that co-express the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit and the calcium-binding protein, calbindin (CB). Both malformed and control cortex of adult (P40-60) animals contained numerous interneurons double-stained for CB and GluR1. Immunoreactivity (IR) for CB was up-regulated in perikarya of interneurons within supragranular layers of control cortex between P12 and P40. However, in malformed adult (P40) cortex, CB-IR levels were significantly lower than in adult controls, and fell midway between levels in immature and adult control animals. Between P12 and P40, GluR1-IR was down-regulated in perikarya of interneurons in control cortex. Somatic GluR1-IR levels in malformed adult (P40) cortex were not different from adult controls. These neurons formed a dense plexus of highly GluR1-positive spiny dendrites within layer II. The dendritic plexus in the malformation was more intensely GluR1-immunoreactive than that in layer II of control cortex. This was due to apparent changes in thickness and length of dendrites, rather than to significant changes in the number of interneuronal perikarya in the microgyral cortex. Results indicate that the population of GluR1/CB-containing interneurons is spared in malformed microgyral cortex, but that these cells sustain lasting decreases in their somatic expression of calbindin and alterations of dendritic structure. Potential functional implications of these findings are discussed.
出生后第一天或第二天（P0 - 1）受到损伤的大鼠新皮层会发展出一种致痫性的、层状异常的畸形，称为微小脑回。为了研究这种发育可塑性对抑制性中间神经元的影响，我们研究了共同表达α - 氨基 - 3 - 羟基 - 5 - 甲基异恶唑 - 4 - 丙酸受体GluR1亚基和钙结合蛋白钙结合蛋白（CB）的GABA能细胞亚群。成年（P40 - 60）动物的畸形和对照皮层都含有大量CB和GluR1双染的中间神经元。在P12和P40之间，对照皮层颗粒上层中间神经元的胞体中CB的免疫反应性（IR）上调。然而，在畸形成年（P40）皮层中，CB - IR水平显著低于成年对照，且介于未成熟和成年对照动物的水平之间。在P12和P40之间，对照皮层中间神经元的胞体中GluR1 - IR下调。畸形成年（P40）皮层中神经元胞体的GluR1 - IR水平与成年对照无差异。这些神经元在第二层内形成了一个高度GluR1阳性的棘状树突密集丛。畸形中的树突丛比对照皮层第二层中的树突丛具有更强的GluR1免疫反应性。这是由于树突的厚度和长度明显变化，而不是微小脑回皮层中中间神经元胞体数量的显著变化。结果表明，含有GluR1/CB的中间神经元群体在畸形微小脑回皮层中未受影响，但这些细胞的钙结合蛋白体细胞表达持续下降，且树突结构发生改变。讨论了这些发现的潜在功能意义。
