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.

在整个感觉系统中，时间频率信息沿着上升的中央通路逐渐转换。尽管为阐明这些转变的机制基础付出了相当大的努力，但它们仍然知之甚少。在这里，我们使用了一系列新方法，包括体内全细胞记录和局部药理学操作，以及识别由激发、抑制和活性膜特性引起的电导的新计算算法，以阐明中脑听觉神经元选择性的潜在机制对于较长的时间间隔。令人惊讶的是，我们发现刺激驱动的激发可以增加而选择性降低在用gabazine或氟化物的细胞内递送减弱抑制后。我们提出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，即对细胞的激发显示出比实际情况更大的时间选择性。我们还表明，在减弱抑制后，可以降低兴奋的速率依赖性抑制，这是长间隔选择性的重要组成部分。这些新发现表明非线性分流抑制在塑造激励的幅度和间隔选择性方面起着关键作用。我们的研究结果为理解大脑如何解码间隔提供了重大进展，并可以解释先前报道的中脑神经元激发的矛盾时间选择性。