Early life sleep disruption alters glutamate and dendritic spines in prefrontal cortex and impairs cognitive flexibility in prairie voles.
Early life sleep disruption alters glutamate and dendritic spines in prefrontal cortex and impairs cognitive flexibility in prairie voles.
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DOI：
10.1016/j.crneur.2021.100020
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发表时间：
2021-01-01
期刊：
影响因子：
--
通讯作者：
Lim, Miranda M
中科院分区：
文献类型：
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作者：
Jones, Carolyn E;Chau, Alex Q;Lim, Miranda M
早期的生活经历对于大脑中兴奋性突触的正确组织至关重要，对成熟较晚的经验依赖性区域（如内侧前额叶皮层（mPFC））有着巨大的影响。我们实验室以前的工作表明，在高度社会化的草原田鼠中，出生后14-21天的早期生活睡眠中断（ELSD）会导致社会行为的长期损害。在这里，我们进一步假设ELSD改变mPFC中的神经元突触，从而影响认知灵活性，这是一种mPFC依赖性行为。ELSD导致受损的线索恐惧消退（表明认知能力），树突棘密度增加，并减少囊泡谷氨酸转运蛋白1（vGLUT 1）标记的突触前神经末梢内mPFC的谷氨酸免疫金标记。我们的研究结果对人类的神经发育障碍具有深远的意义，例如自闭症谱系障碍，也显示睡眠不良，社会行为受损，认知能力，以及mPFC中树突棘密度和谷氨酸变化的改变，并暗示睡眠不良可能导致这些变化。
Early life experiences are crucial for proper organization of excitatory synapses within the brain, with outsized effects on late-maturing, experience-dependent regions such as the medial prefrontal cortex (mPFC). Previous work in our lab showed that early life sleep disruption (ELSD) from postnatal days 14-21 in the highly social prairie vole results in long lasting impairments in social behavior. Here, we further hypothesized that ELSD alters glutamatergic synapses in mPFC, thereby affecting cognitive flexibility, an mPFC-dependent behavior. ELSD caused impaired cued fear extinction (indicating cognitive inflexibility), increased dendritic spine density, and decreased glutamate immunogold-labeling in vesicular glutamate transporter 1 (vGLUT1)-labeled presynaptic nerve terminals within mPFC. Our results have profound implications for neurodevelopmental disorders in humans such as autism spectrum disorder that also show poor sleep, impaired social behavior, cognitive inflexibility, as well as altered dendritic spine density and glutamate changes in mPFC, and imply that poor sleep may cause these changes.