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 such as autism spectrum disorder. 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 the developmental overproduction of cortical superficial neurons impairs auditory processing in mice. We took advantage of a WNT/β- catenin signaling inhibitor, XAV939, to overproduce cortical superficial excitatory neurons during development. XAV939-treated adult mice exhibited a longer reaction time and a higher threshold to detect acoustic stimuli behaviorally. This mouse model also demonstrated abnormal auditory cortical processing depending on experimental conditions: in a passive listening condition, we observed lower beta power and lower spontaneous and auditory-evoked activity in putative excitatory cells whereas higher pre-stimulus spontaneous activity in excitatory cells is associated with failing to detect auditory stimuli behaviorally. On the other hand, the auditory thalamus did not show any significant difference in neural firing between XAV939-treated and control groups. Furthermore, functional monosynaptic connections were significantly reduced between cortical putative excitatory cells. Altogether, our results suggest that the atypical auditory detectability of XAV939-treated animals can be explained by abnormal auditory cortical processing. 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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
The original manuscript has been revised thoroughly. All figures were updated.
