■在患有严重听觉障碍的患者中,可以通过用于电刺激中枢神经系统的感觉假体来实现部分听力恢复。然而,这些最先进的方法遭受有限的光谱分辨率:电场扩展取决于周围介质的阻抗,阻碍神经组织中的空间聚焦电刺激。为了克服这些限制,光遗传学激活可以应用于此类假体中,以通过对附近神经元集合的精确和差异刺激来实现增强的分辨率。先前的实验为啮齿动物听觉系统中光遗传激活的行为检测提供了第一个证据,但是对于涉及差异激活的复杂和行为相关的感觉模式的产生知之甚少。
■在这项研究中,我们开发了光遗传学植入物并对其进行了行为测试,以激发鼠下丘(ICc)的两个空间分离的点。
■使用基于奖励的操作Go/No-Go范式,我们表明,皮层下感觉通路的差异光遗传学激活是可能且有效的。我们展示了以前在频率辨别范式(a)中训练过的动物如何对声音或光遗传刺激做出快速反应,(b)通常检测两个不同神经元集合的光遗传学刺激,(c)区分它们。
■我们的结果表明,在ICctonotopy的不同点处的光遗传学兴奋性刺激在几个月的时间段内引起稳定的响应行为。通过这项研究,我们为在自由移动的动物中使用复杂的人工线索对感觉系统进行皮层下差异刺激提供了第一个原理证明。
UNASSIGNED: In patients with severe auditory impairment, partial hearing restoration can be achieved by sensory prostheses for the electrical stimulation of the central nervous system. However, these state-of-the-art approaches suffer from limited spectral resolution: electrical field spread depends on the impedance of the surrounding medium, impeding spatially focused electrical stimulation in neural tissue. To overcome these limitations, optogenetic activation could be applied in such prostheses to achieve enhanced resolution through precise and differential stimulation of nearby neuronal ensembles. Previous experiments have provided a first proof for behavioral detectability of optogenetic activation in the rodent auditory system, but little is known about the generation of complex and behaviorally relevant sensory patterns involving differential activation.
UNASSIGNED: In this study, we developed and behaviorally tested an optogenetic implant to excite two spatially separated points along the tonotopy of the murine inferior colliculus (ICc).
UNASSIGNED: Using a reward based operant Go/No-Go paradigm, we show that differential optogenetic activation of a sub-cortical sensory pathway is possible and efficient. We demonstrate how animals which were previously trained in a frequency discrimination paradigm (a) rapidly respond to either sound or optogenetic stimulation, (b) generally detect optogenetic stimulation of two different neuronal ensembles, and (c) discriminate between them.
UNASSIGNED: Our results demonstrate that optogenetic excitatory stimulation at different points of the ICc tonotopy elicits a stable response behavior over time periods of several months. With this study, we provide the first proof of principle for sub-cortical differential stimulation of sensory systems using complex artificial cues in freely moving animals.