使用ChR2传递时变刺激
Delivery of time-varying stimuli using ChR2
摘要:
为了了解神经元群体的感觉处理,有必要将刺激传递到动物的感觉器官并记录下游诱发的群体活动。然而,从感觉输入到细胞中的突触电流的通路是复杂的,这些细胞是从感觉器官移除的几个突触。来自其他大脑区域的内在噪声和不受控制的调制输入会干扰明确定义的刺激的传递。在这里,我们调查的能力通道视紫红质提供精确的随时间变化的电流,神经元在任何一点沿感觉运动通路。为了做到这一点,我们首先推导出的通道视紫红质-2(ChR 2)的振幅响应函数,使用三态马尔可夫通道动力学模型。通过生物医学上真实的参数,该函数支持相对宽的信号通带并包含共振。我们确认我们预测的振幅响应函数的有效性,使用时变光学刺激的兴奋性神经元,表达野生型ChR 2或ChR 2(H134 R)突变体。总之,我们的研究结果表明,ChR 2衍生的光遗传学工具可用于在生理相关的频带上向遗传指定的群体提供可重复的时变电流。
英文摘要:
To understand sensory processing in neuronal populations, it is necessary to deliver stimuli to the sensory organs of animals and record evoked population activity downstream. However, the pathways from sensory input to synaptic currents in cells that are several synapses removed from sensory organs are complex. Intrinsic noise and uncontrolled modulatory input from other brain regions can interfere with the delivery of well-defined stimuli. Here we investigate the ability of channelrhodopsins to deliver precise time-varying currents to neurons at any point along the sensory-motor pathway. To do this, we first deduce the amplitude response function of channelrhodopsin-2 (ChR2) using a three state Markov model of channel kinetics. With biophysically realistic parameters, this function supports a relatively broad signal passband and contains a resonance. We confirm the validity of our predicted amplitude response function using time-varying optical stimulation of excitatory neurons that express either wild type ChR2 or the ChR2(H134R) mutant. Together, our results indicate that ChR2-derived optogenetic tools are useful for delivering repeatable, time-varying currents to genetically-specified populations over a physiologically-relevant frequency band.
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