Harmonics are an integral part of music, speech, and vocalizations of animals. Since the rest of the auditory environment is primarily made up of nonharmonic sounds, the auditory system needs to perceptually separate the above two kinds of sounds. In mice, harmonics, generally with two-tone components (two-tone harmonic complexes, TTHCs), form an important component of vocal communication. Communication by pups during isolation from the mother and by adult males during courtship elicits typical behaviors in female mice—dams and adult courting females, respectively. Our study shows that the processing of TTHC is specialized in mice providing neural basis for perceptual differences between tones and TTHCs and also nonharmonic sounds. Investigation of responses in the primary auditory cortex (Au1) from in vivo extracellular recordings and two-photon Ca²⁺ imaging of excitatory and inhibitory neurons to TTHCs exhibit enhancement, suppression, or no-effect with respect to tones. Irrespective of neuron type, harmonic enhancement is maximized, and suppression is minimized when the fundamental frequencies (F₀) match the neuron's best fundamental frequency (BF₀). Sex-specific processing of TTHC is evident from differences in the distributions of neurons’ best frequency (BF) and best fundamental frequency (BF₀) in single units, differences in harmonic suppressed cases re-BF₀, independent of neuron types, and from pairwise noise correlations among excitatory and parvalbumin inhibitory interneurons. Furthermore, TTHCs elicit a higher response compared with two-tone nonharmonics in females, but not in males. Thus, our study shows specialized neural processing of TTHCs over tones and nonharmonics, highlighting local network specialization among different neuronal types.

谐波是动物音乐、语音和发声不可或缺的一部分。由于听觉环境的其余部分主要由非谐波声音组成，因此听觉系统需要在感知上将上述两种声音分开。在小鼠中，谐波通常具有双音分量（双音谐波复合体，TTHC），是人声交流的重要组成部分。幼崽在与母亲隔离期间的交流和成年雄性在求偶期间的交流会引起雌性小鼠的典型行为——分别是母鼠和成年求偶雌鼠。我们的研究表明，TTHC 的加工专门针对小鼠，为音调和 TTHC 之间的感知差异以及非谐波声音提供神经基础。来自体内细胞外记录的初级听觉皮层 （Au1） 反应的研究以及兴奋性和抑制性神经元对 TTHC 的双光子 Ca²⁺ 成像在音调方面表现出增强、抑制或无影响。无论神经元类型如何，当基频 （F₀） 与神经元的最佳基频 （BF₀） 匹配时，谐波增强都会最大化，抑制也会最小化。TTHC 的性别特异性加工从神经元最佳频率 （BF） 和最佳基频 （BF₀） 在单个单位中的分布差异、谐波抑制情况 re-BF₀ 的差异（与神经元类型无关）以及兴奋性和小白蛋白抑制性中间神经元之间的成对噪声相关性中显而易见。此外，与女性的双音非谐波相比，TTHC 引起的响应更高，但在男性中则没有。 因此，我们的研究表明 TTHC 在音调和非谐波上的专业化神经处理，突出了不同神经元类型之间的局部网络专业化。