Hartwig Cortnie L, Worrell Jason, Levine Richard B, Ramaswami Mani, Sanyal Subhabrata
Graduate Program in Physiological Sciences, University of Arizona, Tucson, Arizona 85721, USA.
Dev Neurobiol. 2008 Sep 1;68(10):1225-42. doi: 10.1002/dneu.20655.
During learning and memory formation, information flow through networks is regulated significantly through structural alterations in neurons. Dendrites, sites of signal integration, are key targets of activity-mediated modifications. Although local mechanisms of dendritic growth ensure synapse-specific changes, global mechanisms linking neural activity to nuclear gene expression may have profound influences on neural function. Fos, being an immediate-early gene, is ideally suited to be an initial transducer of neural activity, but a precise role for the AP-1 transcription factor in dendrite growth remains to be elucidated. Here we measure changes in the dendritic fields of identified Drosophila motor neurons in vivo and in primary culture to investigate the role of the immediate-early transcription factor AP-1 in regulating endogenous and activity-induced dendrite growth. Our data indicate that (a) increased neural excitability or depolarization stimulates dendrite growth, (b) AP-1 (a Fos, Jun hetero-dimer) is required for normal motor neuron dendritic growth during development and in response to activity induction, and (c) neuronal Fos protein levels are rapidly but transiently induced in motor neurons following neural activity. Taken together, these results show that AP-1 mediated transcription is important for dendrite growth, and that neural activity influences global dendritic growth through a gene-expression dependent mechanism gated by AP-1.
在学习和记忆形成过程中,通过神经元的结构改变,信息流在神经网络中的传递受到显著调节。树突作为信号整合的位点,是活性介导修饰的关键靶点。尽管树突生长的局部机制确保了突触特异性变化,但将神经活动与核基因表达联系起来的全局机制可能对神经功能产生深远影响。Fos作为一种即早基因,非常适合作为神经活动的初始转导因子,但AP-1转录因子在树突生长中的精确作用仍有待阐明。在这里,我们在体内和原代培养中测量了已鉴定的果蝇运动神经元树突场的变化,以研究即早转录因子AP-1在调节内源性和活性诱导的树突生长中的作用。我们的数据表明:(a)神经兴奋性增加或去极化刺激树突生长;(b)AP-1(一种Fos、Jun异源二聚体)在发育过程中以及对活性诱导的反应中,是正常运动神经元树突生长所必需的;(c)神经活动后,运动神经元中的神经元Fos蛋白水平迅速但短暂地被诱导。综上所述,这些结果表明,AP-1介导的转录对树突生长很重要,并且神经活动通过由AP-1控制的基因表达依赖性机制影响全局树突生长。