A new genetic model of activity-induced Ras signaling dependent pre-synaptic plasticity in Drosophila.
A new genetic model of activity-induced Ras signaling dependent pre-synaptic plasticity in Drosophila.
复制标题
DOI：
10.1016/j.brainres.2010.02.061
复制
发表时间：
2010-04-22
期刊：
影响因子：
2.9
通讯作者：
Sanyal, Subhabrata
中科院分区：
文献类型：
--
作者：
Freeman, Amanda;Bowers, Mallory;Mortimer, Alysia Vrailas;Timmerman, Christina;Roux, Stephanie;Ramaswami, Mani;Sanyal, Subhabrata
在体内诱导活性依赖性神经元可塑性的技术允许在其生物学背景下研究潜在的信号传导途径。在这里，我们证明了活动诱导的可塑性在果蝇的昏迷（NSF突变体）和Kum（SERCA突变体）的神经肌肉突触双突变体，并提出了一个分析的潜在信号通路。comt; Kum（CK）双突变体在正常培养条件下表现出运动活性增加，伴随着更大的神经肌肉接头突触和稳定升高的诱发递质释放。在CK突变体中观察到的突触大小和递质释放的增强被以下因素完全消除：a）运动神经元活性降低; B）Ras/ERK信号级联减弱;或c）转录因子Fos和CREB抑制。所有这些都将突触特性限制在接近野生型水平。总之，这些结果证明了CK动物运动突触的神经活性依赖性可塑性，这需要Ras/ERK信号传导和Fos和CREB的正常转录活性。此外，神经元Ras活化和Fos转录的新型体内报告物也证实了CK动物运动神经元中通过Ras/AP-1途径的信号传导增加，这与我们的遗传实验结果一致。因此，本研究：a）提供了一种在体内研究活性诱导的突触可塑性的稳健系统; B）在果蝇幼虫的突触能运动神经元中建立了神经活性、Ras信号传导、转录调节和突触前可塑性之间的因果联系;以及c）提供了果蝇中Ras和AP-1依赖性信号传导途径的新的遗传编码的报告物。
Techniques to induce activity-dependent neuronal plasticity in vivo allow the underlying signaling pathways to be studied in their biological context. Here, we demonstrate activity-induced plasticity at neuromuscular synapses of Drosophila double mutant for comatose (an NSF mutant) and Kum (a SERCA mutant), and present an analysis of the underlying signaling pathways. comt; Kum (CK) double mutants exhibit increased locomotor activity under normal culture conditions, concomitant with a larger neuromuscular junction synapse and stably elevated evoked transmitter release. The observed enhancements of synaptic size and transmitter release in CK mutants are completely abrogated by: a) reduced activity of motor neurons; b) attenuation of the Ras/ERK signaling cascade; or c) inhibition of the transcription factors Fos and CREB. all of which restrict synaptic properties to near wild type levels. Together, these results document neural activity-dependent plasticity of motor synapses in CK animals that requires Ras/ERK signaling and normal transcriptional activity of Fos and CREB. Further, novel in vivo reporters of neuronal Ras activation and Fos transcription also confirm increased signaling through a Ras/AP-1 pathway in motor neurons of CK animals, consistent with results from our genetic experiments. Thus, this study: a) provides a robust system in which to study activity-induced synaptic plasticity in vivo; b) establishes a causal link between neural activity, Ras signaling, transcriptional regulation and pre-synaptic plasticity in glutamatergic motor neurons of Drosophila larvae; and c) presents novel, genetically encoded reporters for Ras and AP-1 dependent signaling pathways in Drosophila.
登录
查看更多内容
影响因子：
4.8
作者：
Bivona, TG;Philips, MR
通讯作者：
Philips, MR
影响因子：
11.4
作者：
Eresh, S;Riese, J;Bienz, M
通讯作者：
Bienz, M
影响因子：
56.9
作者：
BADING, H;GINTY, DD;GREENBERG, ME
通讯作者：
GREENBERG, ME
影响因子：
3.4
作者：
Godenschwege, TA;Reisch, D;Buchner, E
通讯作者：
Buchner, E
影响因子：
16.2
作者：
Budnik, V;Koh, YH;Gorczyca, M
通讯作者：
Gorczyca, M