Inhibitory gating of coincidence-dependent sensory binding in secondary auditory cortex

Amber M Kline,Destinee A Aponte,Hiroyuki K Kato,Andrea Giovannucci,Hiroaki Tsukano

doi:10.1038/s41467-021-24758-6

Amber M Kline, Destinee A Aponte + Show 3 more

Open Access

https://doi.org/10.1038/s41467-021-24758-6

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Abstract

Integration of multi-frequency sounds into a unified perceptual object is critical for recognizing syllables in speech. This “feature binding” relies on the precise synchrony of each component’s onset timing, but little is known regarding its neural correlates. We find that multi-frequency sounds prevalent in vocalizations, specifically harmonics, preferentially activate the mouse secondary auditory cortex (A2), whose response deteriorates with shifts in component onset timings. The temporal window for harmonics integration in A2 was broadened by inactivation of somatostatin-expressing interneurons (SOM cells), but not parvalbumin-expressing interneurons (PV cells). Importantly, A2 has functionally connected subnetworks of neurons preferentially encoding harmonic over inharmonic sounds. These subnetworks are stable across days and exist prior to experimental harmonics exposure, suggesting their formation during development. Furthermore, A2 inactivation impairs performance in a discrimination task for coincident harmonics. Together, we propose A2 as a locus for multi-frequency integration, which may form the circuit basis for vocal processing.

Highlights

Integration of multi-frequency sounds into a unified perceptual object is critical for recognizing syllables in speech
To design harmonic stimuli that are representative of what mice experience in their natural environment, we first determined the range of F0s used in their harmonic vocalizations
To examine if preferential activation of A2 is specific to this vocalization or generalized to harmonic structures, we presented artificially generated harmonics (F0 = 2, 4, and 8 kHz, harmonic stacks up to 40 kHz)

Summary

Introduction

Integration of multi-frequency sounds into a unified perceptual object is critical for recognizing syllables in speech. Previous studies have found neurons in both primary and higherorder cortices that show preferential firing to combinations of frequencies over simple pure tones[16,17,18,19,20] It remains unknown whether the activity of these neurons shares the same critical properties of perceptual binding in human psychophysics, such as synchrony dependence, and how they contribute to perceptual behaviors. To address this gap in knowledge and identify the primary locus of integration, we focused on harmonics, a key sound feature in animal vocalizations that consists of integer multiples of a fundamental frequency (F0). Taking advantage of two-photon calcium imaging, optogenetics, and electrophysiology in awake mice, we investigated the circuit mechanisms that enable perceptual binding of behaviorally relevant harmonic sounds

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