Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
Neurobiol Dis. 2010 May;38(2):281-7. doi: 10.1016/j.nbd.2010.01.018. Epub 2010 Feb 4.
Motor and cognitive functions are severely impaired in Rett syndrome (RTT). Here, we examined local synaptic circuits of layer 2/3 (L2/3) pyramidal neurons in motor-frontal cortex of male hemizygous MeCP2-null mice at 3 to 4weeks of age. We mapped local excitatory input to L2/3 neurons using glutamate uncaging and laser scanning photostimulation, and compared synaptic input maps recorded from MeCP2-null and wild type (WT) mice. Local excitatory input was significantly reduced in the mutants. The strongest phenotype was observed for lateral (horizontal, intralaminar) inputs, that is, L2/3-->2/3 inputs, which showed a large reduction in MeCP2(-/y) animals. Neither the amount of local inhibitory input to these L2/3 pyramidal neurons nor their intrinsic electrophysiological properties differed by genotype. Our findings provide further evidence that excitatory networks are selectively reduced in RTT. We discuss our findings in the context of recently published parallel studies using selective MeCP2 knockdown in individual L2/3 neurons.
运动和认知功能在雷特综合征（RTT）中严重受损。在这里，我们研究了雄性半合子 MeCP2 缺失小鼠运动前皮质 L2/3（L2/3）锥体神经元的局部突触回路，这些小鼠在 3 至 4 周龄时。我们使用谷氨酸解笼和激光扫描光刺激来绘制 L2/3 神经元的局部兴奋性输入，并比较了从 MeCP2 缺失型和野生型（WT）小鼠记录的突触输入图。在突变体中，局部兴奋性输入明显减少。在外侧（水平，层内）输入，即 L2/3-->2/3 输入中观察到最强的表型，MeCP2（-/y）动物的输入明显减少。这些 L2/3 锥体神经元的局部抑制性输入量或其内在电生理特性在基因型上没有差异。我们的研究结果进一步证明兴奋性网络在 RTT 中选择性减少。我们在最近发表的使用个体 L2/3 神经元选择性 MeCP2 敲低的平行研究中讨论了我们的发现。
