Nitric oxide mediates activity-dependent change to synaptic excitation during a critical period in Drosophila.
Nitric oxide mediates activity-dependent change to synaptic excitation during a critical period in Drosophila.
复制标题
一氧化氮介导果蝇关键时期突触兴奋的活动依赖性变化。
DOI：
10.1038/s41598-021-99868-8
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发表时间：
2021-10-13
影响因子：
4.6
通讯作者：
Baines RA
中科院分区：
文献类型：
--
作者：
Giachello CNG;Fan YN;Landgraf M;Baines RA
神经系统发育过程中协调网络功能的出现通常与关键时期有关。这些阶段对关键期内的活动扰动很敏感，但在关键期之外则不然，这可能导致网络功能永久改变，原因尚不清楚。特别是，抑制神经元活动以调节神经元生理学或结构变化的机制尚不清楚。在这里，我们利用最近确定的无脊椎动物模型研究的关键时期，果蝇幼虫运动系统。在这一关键时期操纵神经元活动足以增加突触兴奋，并永久地使运动网络易于诱发癫痫发作。使用遗传学和药理学操作，我们确定一氧化氮（NO）信号作为活动的关键介质。在关键期短暂增加或减少NO信号模拟活动操纵的影响，引起突触传递和癫痫发作诱导易感性的相同持久变化。此外，活动增加对发育中的网络的影响被伴随的NO信号传导的减少所抑制，并被额外的NO信号传导所增强。这些数据将NO信号确定为下游效应器，为关键时期的活动如何调节发育中的网络提供了新的机制见解。
The emergence of coordinated network function during nervous system development is often associated with critical periods. These phases are sensitive to activity perturbations during, but not outside, of the critical period, that can lead to permanently altered network function for reasons that are not well understood. In particular, the mechanisms that transduce neuronal activity to regulating changes in neuronal physiology or structure are not known. Here, we take advantage of a recently identified invertebrate model for studying critical periods, the Drosophila larval locomotor system. Manipulation of neuronal activity during this critical period is sufficient to increase synaptic excitation and to permanently leave the locomotor network prone to induced seizures. Using genetics and pharmacological manipulations, we identify nitric oxide (NO)-signaling as a key mediator of activity. Transiently increasing or decreasing NO-signaling during the critical period mimics the effects of activity manipulations, causing the same lasting changes in synaptic transmission and susceptibility to seizure induction. Moreover, the effects of increased activity on the developing network are suppressed by concomitant reduction in NO-signaling and enhanced by additional NO-signaling. These data identify NO signaling as a downstream effector, providing new mechanistic insight into how activity during a critical period tunes a developing network.
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影响因子：
5.3
作者：
Lillis, Kyle P.;Wang, Zemin;Staley, Kevin J.
通讯作者：
Staley, Kevin J.
影响因子：
4.6
作者：
Marley R;Giachello CN;Scrutton NS;Baines RA;Jones AR
通讯作者：
Jones AR
DOI：
10.1016/b978-0-12-804066-9.00024-9
发表时间：
2017-01-01
期刊：
MODELS OF SEIZURES AND EPILEPSY, 2ND EDITION
影响因子：
--
作者：
Baines, Richard A.;Giachello, Carlo N. G.;Lin, Wei-Hsiang
通讯作者：
Lin, Wei-Hsiang
影响因子：
5.3
作者：
Gonzalez-Forero, David;Portillo, Federico;Moreno-Lopez, Bernardo
通讯作者：
Moreno-Lopez, Bernardo
DOI：
10.1073/pnas.1416586112
发表时间：
2015-02-17
影响因子：
11.1
作者：
Fogle, Keri J.;Baik, Lisa S.;Holmes, Todd C.
通讯作者：
Holmes, Todd C.