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Selective and quickly reversible inactivation of mammalian neurons in vivo using the Drosophila allatostatin receptor.

机译:使用果蝇阿托他汀受体选择性和快速可逆的体内灭活哺乳动物神经元。

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摘要

Genetic strategies for perturbing activity of selected neurons hold great promise for understanding circuitry and behavior. Several such strategies exist, but there has been no direct demonstration of reversible inactivation of mammalian neurons in vivo. We previously reported quickly reversible inactivation of neurons in vitro using expression of the Drosophila allatostatin receptor (AlstR). Here, adeno-associated viral vectors are used to express AlstR in vivo in cortical and thalamic neurons of rats, ferrets, and monkeys. Application of the receptor's ligand, allatostatin (AL), leads to a dramatic reduction in neural activity, including responses of visual neurons to optimized visual stimuli. Additionally, AL eliminates activity in spinal cords of transgenic mice conditionally expressing AlstR. This reduction occurs selectively in AlstR-expressing neurons. Inactivation can be reversed within minutes upon washout of the ligand and is repeatable, demonstrating that the AlstR/AL system is effective forselective, quick, and reversible silencing of mammalian neurons in vivo.
机译:扰动选定神经元活动的遗传策略对理解电路和行为具有广阔的前景。存在几种这样的策略,但是没有直接证明体内哺乳动物神经元可逆失活。我们以前报道了使用果蝇alotastatin受体(AlstR)的表达在体外快速可逆的灭活神经元。在这里,腺相关病毒载体用于在大鼠,雪貂和猴子的皮层和丘脑神经元中体内表达AlstR。受体配体阿托他汀(AL)的应用导致神经活动的急剧减少,包括视觉神经元对最佳视觉刺激的反应。另外,AL消除了有条件表达AlstR的转基因小鼠脊髓中的活性。这种减少选择性地在表达AlstR的神经元中发生。灭活配体后几分钟内就可以逆转,并且是可重复的,这表明AlstR / AL系统对于体内哺乳动物神经元的选择性,快速和可逆沉默是有效的。

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