Activity-dependent homeostatic specification of transmitter expression in embryonic neurons
Activity-dependent homeostatic specification of transmitter expression in embryonic neurons
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DOI：
10.1038/nature02518
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发表时间：
2004-06-03
期刊：
影响因子：
64.8
通讯作者：
Spitzer, NC
中科院分区：
文献类型：
--
作者：
Borodinsky, LN;Root, CM;Spitzer, NC
神经递质对于神经元间的信号传递是必不可少的，而在分化神经元过程中合适的递质的指定与神经元的内在特性和外在信号蛋白有关。在这里，我们表明，改变不同类型的胚胎脊髓神经元在体内自发产生的不同的钙尖峰活动模式，改变神经元表达的递质，而不影响细胞身份标志的表达。调节似乎是动态平衡的：抑制活动会导致表达兴奋性递质的神经元数量增加，表达抑制性递质的神经元数量减少；当活动增强时，情况正好相反。在体外施加特定的尖峰频率不会影响细胞身份的标记，但在早期的关键时期，再次指定不适合于它们所表达的标记的递质的表达。这一结果确定了模式活动在中枢神经系统发育中的新作用。
Neurotransmitters are essential for interneuronal signalling, and the specification of appropriate transmitters in differentiating neurons has been related to intrinsic neuronal identity and to extrinsic signalling proteins. Here we show that altering the distinct patterns of Ca2+ spike activity spontaneously generated by different classes of embryonic spinal neurons in vivo changes the transmitter that neurons express without affecting the expression of markers of cell identity. Regulation seems to be homeostatic: suppression of activity leads to an increased number of neurons expressing excitatory transmitters and a decreased number of neurons expressing inhibitory transmitters; the reverse occurs when activity is enhanced. The imposition of specific spike frequencies in vitro does not affect labels of cell identity but again specifies the expression of transmitters that are inappropriate for the markers they express, during an early critical period. The results identify a new role of patterned activity in development of the central nervous system.