Mangin Jean-Marie, Kunze Albrecht, Chittajallu Ramesh, Gallo Vittorio
Department of Neurology, Center for Neuroscience Research, Children's National Medical Center, Washington, DC 20010, USA.
J Neurosci. 2008 Jul 23;28(30):7610-23. doi: 10.1523/JNEUROSCI.1355-08.2008.
Several studies have provided evidence that NG2-expressing (NG2(+)) progenitor cells are anatomically associated to neurons in gray matter areas. By analyzing the spatial distribution of NG2(+) cells in the hilus of the mouse dentate gyrus, we demonstrate that NG2(+) cells are indeed closely associated to interneurons. To define whether this anatomical proximity reflected a specific physiological interaction, we performed patch-clamp recordings on hilar NG2(+) cells and interneurons between 3 and 21 postnatal days. We first observed that hilar NG2(+) cells exhibit spontaneous glutamatergic EPSCs (sEPSCs) whose frequency and amplitude increase during the first 3 postnatal weeks. At the same time, the rise time and decay time of sEPSCs significantly decreased, suggesting that glutamatergic synapses in NG2(+) cells undergo a maturation process that is reminiscent of what has been reported in neurons during the same time period. We also observed that hilar interneurons and associated NG2(+) cells are similarly integrated into the local network, receiving excitatory inputs from both granule cells and CA3 pyramidal neurons. By performing pair recordings, we found that bursts of activity induced by GABAergic antagonists were strongly synchronized between both cell types and that the amplitude of these bursts was positively correlated. Finally, by applying carbachol to increase EPSC activity, we observed that closely apposed cells were more likely to exhibit synchronized EPSCs than cells separated by >200 microm. The finding that NG2(+) cells are sensing patterns of activity arising in closely associated neurons suggests that NG2(+) cell function is finely regulated by the local network.
多项研究已提供证据表明,表达NG2的(NG2(+))祖细胞在解剖学上与灰质区域的神经元相关联。通过分析小鼠齿状回门区NG2(+)细胞的空间分布,我们证明NG2(+)细胞确实与中间神经元紧密相关。为了确定这种解剖学上的接近是否反映了特定的生理相互作用,我们在出生后3至21天对门区NG2(+)细胞和中间神经元进行了膜片钳记录。我们首先观察到,门区NG2(+)细胞表现出自发性谷氨酸能兴奋性突触后电流(sEPSCs),其频率和幅度在出生后的前三周增加。同时,sEPSCs的上升时间和衰减时间显著缩短,这表明NG2(+)细胞中的谷氨酸能突触经历了一个成熟过程,这与同一时期神经元中所报道的情况相似。我们还观察到,门区中间神经元和相关的NG2(+)细胞同样被整合到局部网络中,接收来自颗粒细胞和CA3锥体神经元的兴奋性输入。通过进行配对记录,我们发现由GABA能拮抗剂诱导的活动爆发在两种细胞类型之间强烈同步,并且这些爆发的幅度呈正相关。最后,通过应用卡巴胆碱来增加EPSC活性,我们观察到紧密相邻的细胞比相隔>200微米的细胞更有可能表现出同步的EPSCs。NG2(+)细胞能够感知紧密相关神经元中产生的活动模式这一发现表明,NG2(+)细胞的功能受到局部网络的精细调节。