How auditory selectivity for sound timing arises: The diverse roles of GABAergic inhibition in shaping the excitation to interval-selective midbrain neurons.
How auditory selectivity for sound timing arises: The diverse roles of GABAergic inhibition in shaping the excitation to interval-selective midbrain neurons.
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DOI：
10.1016/j.pneurobio.2020.101962
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发表时间：
2021-04
影响因子：
6.7
通讯作者：
Luong K
中科院分区：
文献类型：
--
作者：
Alluri RK;Rose GJ;Leary CJ;Palaparthi A;Hanson JL;Vasquez-Opazo GA;Graham JA;Luong K
在整个感觉系统中，时间频率信息沿着沿着上升的中枢通路逐渐转换。尽管相当大的努力来阐明这些转变的机制基础，他们仍然知之甚少。在这里，我们使用了一种新的星座的方法，包括全细胞记录和局灶性药理学操作，在体内，和新的计算算法，识别电导产生的兴奋，抑制和活性膜的属性，阐明机制的选择性中脑听觉神经元的长时间间隔。令人惊讶的是，我们发现，刺激驱动的兴奋可以增加，其选择性降低以下衰减的抑制与加巴嗪或细胞内交付的氟化物。我们建议，这种非线性相互作用是由于分流抑制。这种抑制的速率依赖性导致了一种错觉，即对细胞的兴奋表现出比实际情况更大的时间选择性。我们还表明，率依赖性抑制的兴奋，长间隔选择性的重要组成部分，可以减少衰减抑制后。这些新的发现表明，非线性分流抑制在塑造兴奋的幅度和间隔选择性中起着关键作用。我们的研究结果提供了一个重大的进步，了解大脑如何解码的时间间隔，并可能解释矛盾的时间选择性兴奋中脑神经元先前报道。
Across sensory systems, temporal frequency information is progressively transformed along ascending central pathways. Despite considerable effort to elucidate the mechanistic basis of these transformations, they remain poorly understood. Here we used a novel constellation of approaches, including whole-cell recordings and focal pharmacological manipulation, in vivo, and new computational algorithms that identify conductances resulting from excitation, inhibition and active membrane properties, to elucidate the mechanisms underlying the selectivity of midbrain auditory neurons for long temporal intervals. Surprisingly, we found that stimulus-driven excitation can be increased and its selectivity decreased following attenuation of inhibition with gabazine or intracellular delivery of fluoride. We propose that this nonlinear interaction is due to shunting inhibition. The rate-dependence of this inhibition results in the illusion that excitation to a cell shows greater temporal selectivity than is actually the case. We also show that rate-dependent depression of excitation, an important component of long-interval selectivity, can be decreased after attenuating inhibition. These novel findings indicate that nonlinear shunting inhibition plays a key role in shaping the amplitude and interval selectivity of excitation. Our findings provide a major advance in understanding how the brain decodes intervals and may explain paradoxical temporal selectivity of excitation to midbrain neurons reported previously.
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