Jones Carolyn E, Chau Alex Q, Olson Randall J, Moore Cynthia, Wickham Peyton T, Puranik Niyati, Guizzetti Marina, Cao Hung, Meshul Charles K, Lim Miranda M
VA Portland Health Care System, Portland, OR, USA.
Oregon Health & Science University, Portland, OR, USA.
Curr Res Neurobiol. 2021;2. doi: 10.1016/j.crneur.2021.100020. Epub 2021 Jul 10.
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.
早期生活经历对于大脑内兴奋性突触的正常组织至关重要，对内侧前额叶皮质（mPFC）等发育较晚、依赖经验的脑区有着巨大影响。我们实验室之前的研究表明，在高度社会化的草原田鼠出生后第14至21天的早期生活睡眠中断（ELSD）会导致社交行为的长期受损。在此，我们进一步推测，ELSD会改变mPFC中的谷氨酸能突触，从而影响认知灵活性，这是一种依赖mPFC的行为。ELSD导致线索性恐惧消退受损（表明认知灵活性受损）、树突棘密度增加，以及mPFC中囊泡谷氨酸转运体1（vGLUT1）标记的突触前神经末梢内谷氨酸免疫金标记减少。我们的研究结果对人类神经发育障碍（如自闭症谱系障碍）具有深远意义，这些疾病也表现出睡眠不佳、社交行为受损、认知灵活性受损，以及mPFC中树突棘密度改变和谷氨酸变化，并暗示睡眠不佳可能导致这些变化。
