Optogenetic polymerization and assembly of electrically functional polymers for modulation of single-neuron excitability.
Optogenetic polymerization and assembly of electrically functional polymers for modulation of single-neuron excitability.
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DOI：
10.1126/sciadv.ade1136
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发表时间：
2022-12-09
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
--
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离子电导率和膜电容是决定神经元兴奋性的两个基本参数。传统的光遗传学已经成为一个强大的工具，暂时操纵膜离子电导率在完整的生物系统。然而，没有类似的方法存在精确操纵细胞膜电容，使神经元兴奋性的持久调制。遗传靶向化学组装的导电和绝缘聚合物可以调节细胞膜电容，但这种技术的进一步发展受到阻碍的时空控制差的聚合物沉积和广泛扩散的过氧化物的细胞毒性。我们解决这些问题，利用遗传靶向光敏剂蛋白组装电功能聚合物在神经元精确的时空控制。使用全细胞膜片钳记录，我们证明了这种光遗传聚合可以实现神经元膜电容和内在兴奋性的逐步调节。此外，细胞毒性可以通过控制光暴露来限制，这证明了一种有前途的精确调节细胞兴奋性的新方法。导电和绝缘聚合物的光遗传组装提供了对膜电容和兴奋性的精确控制。
Ionic conductivity and membrane capacitance are two foundational parameters that govern neuron excitability. Conventional optogenetics has emerged as a powerful tool to temporarily manipulate membrane ionic conductivity in intact biological systems. However, no analogous method exists for precisely manipulating cell membrane capacitance to enable long-lasting modulation of neuronal excitability. Genetically targetable chemical assembly of conductive and insulating polymers can modulate cell membrane capacitance, but further development of this technique has been hindered by poor spatiotemporal control of the polymer deposition and cytotoxicity from the widely diffused peroxide. We address these issues by harnessing genetically targetable photosensitizer proteins to assemble electrically functional polymers in neurons with precise spatiotemporal control. Using whole-cell patch-clamp recordings, we demonstrate that this optogenetic polymerization can achieve stepwise modulation of both neuron membrane capacitance and intrinsic excitability. Furthermore, cytotoxicity can be limited by controlling light exposure, demonstrating a promising new method for precisely modulating cell excitability. Optogenetic assembly of conductive and insulating polymers offers precise control over membrane capacitance and excitability.
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影响因子：
13.9
作者：
Fenno L;Yizhar O;Deisseroth K
通讯作者：
Deisseroth K
影响因子：
2.9
作者：
Al-Nu'airat, Jomana;Altarawneh, Mohammednoor;Dlugogorski, Bogdan Z.
通讯作者：
Dlugogorski, Bogdan Z.
影响因子：
2.9
作者：
BRAIMAN, MS;MOGI, T;ROTHSCHILD, KJ
通讯作者：
ROTHSCHILD, KJ
影响因子：
2.9
作者：
Darmanyan, AP;Jenks, WS;Jardon, P
通讯作者：
Jardon, P
影响因子：
15
作者：
DEMAS, JN;HARRIS, EW;MCBRIDE, RP
通讯作者：
MCBRIDE, RP