Department of Biology, University of Maryland, College Park, MD 20742, USA.
Neuroscience and Cognitive Science Program, University of Maryland, College Park, MD 20742, USA.
Cereb Cortex. 2022 Jun 7;32(12):2575-2589. doi: 10.1093/cercor/bhab365.
The connection between early brain injury and subsequent development of disorders is unknown. Neonatal hypoxia-ischemia (HI) alters circuits associated with subplate neurons (SPNs). SPNs are among the first maturing cortical neurons, project to thalamorecipient layer 4 (L4), and are required for the development of thalamocortical connections. Thus, early HI might influence L4 and such influence might persist. We investigated functional circuits to L4 neurons in neonatal rat HI models of different severities (mild and moderate) shortly after injury and at adolescence. We used laser-scanning photostimulation in slices of auditory cortex during P5-10 and P18-23. Mild injuries did not initially (P6/P7) alter the convergence of excitatory inputs from L2/3, but hyperconnectivity emerged by P8-10. Inputs from L4 showed initial hypoconnectivity which resolved by P8-10. Moderate injuries resulted in initial hypoconnectivity from both layers which resolved by P8-10 and led to persistent strengthening of connections. Inhibitory inputs to L4 cells showed similar changes. Functional changes were mirrored by reduced dendritic complexity. We also observed a persistent increase in similarity of L4 circuits, suggesting that HI interferes with developmental circuit refinement and diversification. Altogether, our results show that neonatal HI injuries lead to persistent changes in intracortical connections.
早期脑损伤与随后发生的疾病之间的关系尚不清楚。新生儿缺氧缺血（HI）改变了与基板神经元（SPN）相关的回路。SPN 是最早成熟的皮质神经元之一，投射到丘脑接受层 4（L4），并发育丘脑皮质连接所必需。因此，早期 HI 可能会影响 L4，并且这种影响可能会持续存在。我们研究了不同严重程度（轻度和中度）的新生大鼠 HI 模型中 L4 神经元的功能回路，分别在损伤后和青春期。我们在 P5-10 和 P18-23 期间使用激光扫描光刺激听觉皮层切片。轻度损伤最初（P6/P7）不会改变来自 L2/3 的兴奋性输入的汇聚，但在 P8-10 时出现超连接。来自 L4 的输入最初表现出连接不足，在 P8-10 时得到解决。中度损伤导致来自两个层的初始连接不足，在 P8-10 时得到解决，并导致连接持续增强。L4 细胞的抑制性输入也显示出类似的变化。功能变化与树突复杂性降低相匹配。我们还观察到 L4 回路的相似性持续增加，这表明 HI 干扰了发育中的回路细化和多样化。总的来说，我们的结果表明，新生儿 HI 损伤会导致皮质内连接持续变化。
