Differential encoding of two-tone harmonics in the male and female mouse auditory cortex

Abstract

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 non-harmonic sounds. Investigation of responses in the primary auditory cortex (Au1) from in-vivo extracellular recordings and 2-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 to two-tone non-harmonics in females, but not in males. Thus, our study shows specialized neural processing of TTHCs over tones and non-harmonics, highlighting local network specialization among different neuronal types.Significance StatementMouse vocalizations have communicative significance, yet the encoding of specific vocalizations in communication contexts is not well understood. To address this question we used two-tone harmonics (TTHCs), a synthetic analogue of the natural harmonics, observed predominantly during mating context and on isolating pups from dams. Our study shows that TTHCs are encoded differently in the primary auditory cortex compared to pure tones, irrespective of neuron type, indicating that TTHCs responses are a fundamental property of neurons similar to their response to pure tones. Additionally, sex specificity was observed, with females exhibiting higher selectivity for harmonics over non-harmonics compared to males, suggesting specialized processing of these calls in females.