Merkler Mirna, Ip Nancy Y, Sakata Shuzo
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow, G4 0RE, UK.
Division of Life Science, State Key Laboratory of Molecular Neuroscience and Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Sci Rep. 2025 Apr 8;15(1):11993. doi: 10.1038/s41598-025-95968-x.
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.
虽然进化过程中的皮质扩张被认为是人类认知能力进化的基础，但过度的发育性扩张会导致巨脑症，这在神经发育障碍中经常出现。然而，关于发育过程中皮质神经元的过度产生如何影响后期生活中的皮质处理和行为，我们知之甚少。在这里，我们表明，发育过程中皮质浅层神经元的过度产生会损害成年小鼠的听觉处理。我们在发育过程中应用XAV939来过度产生皮质浅层兴奋性神经元。经XAV939处理的成年小鼠表现出听觉行为缺陷和异常的听觉皮质处理。此外，我们发现皮质假定兴奋性神经元之间的功能性单突触连接较少。总之，我们的结果表明，异常的听觉皮质处理导致了经XAV939处理的小鼠的非典型听觉可检测性。虽然皮质大小的扩张在进化上是有利的，但发育过程中的异常扩张会对成年期的皮质处理和感知行为产生有害影响。
