Developmental overproduction of cortical superficial neurons impairs adult auditory cortical processing

TL;DR

Overproducing certain brain cells during development in mice leads to hearing problems in adulthood.

Contribution

The study reveals that excessive production of superficial cortical neurons during development impairs adult auditory processing.

Findings

XAV939-treated mice showed auditory behavioral deficits and abnormal auditory cortical processing.

Functional monosynaptic connections between excitatory neurons were reduced in treated mice.

Abnormal auditory cortical processing contributes to atypical auditory detectability in treated mice.

Abstract

While evolutionary cortical expansion is thought to underlie the evolution of human cognitive capabilities, excessive developmental expansion can lead to megalencephaly, often found in neurodevelopmental disorders. Still, little is known about how the overproduction of cortical neurons during development affects cortical processing and behavior in later life. Here we show that developmental overproduction of cortical superficial neurons impairs auditory processing in adult mice. We applied XAV939 to overproduce cortical superficial excitatory neurons during development. XAV939-treated adult mice exhibited auditory behavioral deficits and abnormal auditory cortical processing. Furthermore, we found fewer functional monosynaptic connections between cortical putative excitatory neurons. Altogether, our results suggest that abnormal auditory cortical processing contributes to the atypical auditory detectability in XAV939-treated mice. Although the expansion of cortical size is evolutionarily advantageous, an abnormal expansion during development can result in detrimental effects on cortical processing and perceptual behavior in adulthood.

The online version contains supplementary material available at 10.1038/s41598-025-95968-x.

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