Krsnik Željka, Majić Visnja, Vasung Lana, Huang Hao, Kostović Ivica
Department of Neuroscience, Croatian Institute for Brain Research, School of Medicine, University of ZagrebZagreb, Croatia.
Harvard Medical School, Boston Children's HospitalBoston, MA, USA.
Front Neurosci. 2017 Apr 27;11:233. doi: 10.3389/fnins.2017.00233. eCollection 2017.
Thalamocortical (TH-C) fiber growth begins during the embryonic period and is completed by the third trimester of gestation in humans. Here we determined the timing and trajectories of somatosensory TH-C fibers in the developing human brain. We analyzed the periods of TH-C fiber outgrowth, path-finding, "waiting" in the subplate (SP), target selection, and ingrowth in the cortical plate (CP) using histological sections from post-mortem fetal brain [from 7 to 34 postconceptional weeks (PCW)] that were processed with acetylcholinesterase (AChE) histochemistry and immunohistochemical methods. Images were compared with post mortem diffusion tensor imaging (DTI)-based fiber tractography (code No NO1-HD-4-3368). The results showed TH-C axon outgrowth occurs as early as 7.5 PCW in the ventrolateral part of the thalamic anlage. Between 8 and 9.5 PCW, TH-C axons form massive bundles that traverse the diencephalic-telencephalic boundary. From 9.5 to 11 PCW, thalamocortical axons pass the periventricular area at the pallial-subpallial boundary and enter intermediate zone in radiating fashion. Between 12 and 14 PCW, the TH-C axons, aligned along the fibers from the basal forebrain, continue to grow for a short distance within the deep intermediate zone and enter the deep CP, parallel with SP expansion. Between 14 and 18 PCW, the TH-C interdigitate with callosal fibers, running shortly in the sagittal stratum and spreading through the deep SP ("waiting" phase). From 19 to 22 PCW, TH-C axons accumulate in the superficial SP below the somatosensory cortical area; this occurs 2 weeks earlier than in the frontal and occipital cortices. Between 23 and 24 PCW, AChE-reactive TH-C axons penetrate the CP concomitantly with its initial lamination. Between 25 and 34 PCW, AChE reactivity of the CP exhibits an uneven pattern suggestive of vertical banding, showing a basic 6-layer pattern. In conclusion, human thalamocortical axons show prolonged growth (4 months), and somatosensory fibers precede the ingrowth of fibers destined for frontal and occipital areas. The major features of growing TH-C somatosensory fiber trajectories are fan-like radiation, short runs in the sagittal strata, and interdigitation with the callosal system. These results support our hypothesis that TH-C axons are early factors in SP and CP morphogenesis and synaptogenesis and may regulate cortical somatosensory system maturation.
丘脑皮质（TH-C）纤维的生长始于胚胎期，并在人类妊娠晚期的第三个月完成。在这里，我们确定了发育中的人类大脑中体感TH-C纤维的时间和轨迹。我们使用来自死后胎儿大脑（受孕后7至34周，PCW）的组织切片，通过乙酰胆碱酯酶（AChE）组织化学和免疫组织化学方法，分析了TH-C纤维的长出、寻路、在板下层（SP）“等待”、目标选择以及向皮质板（CP）内生长的时期。将图像与基于死后扩散张量成像（DTI）的纤维束成像（代码编号NO1-HD-4-3368）进行比较。结果显示，TH-C轴突最早在丘脑原基的腹外侧部分于受孕后7.5周开始长出。在8至9.5周之间，TH-C轴突形成大量束状结构，穿过间脑-端脑边界。在9.5至11周之间，丘脑皮质轴突穿过 pallial-subpallial 边界处的脑室周围区域，并以放射状进入中间带。在12至14周之间，沿着来自基底前脑的纤维排列的TH-C轴突在深中间带内继续短距离生长，并与SP扩展平行进入深CP。在14至18周之间，TH-C与胼胝体纤维相互交错，在矢状层中短暂运行并穿过深SP（“等待”阶段）。在19至22周之间，TH-C轴突聚集在体感皮质区域下方的浅SP中；这比额叶和枕叶皮质早2周发生。在23至24周之间，AChE反应性的TH-C轴突伴随着CP的初始分层穿透CP。在25至34周之间，CP的AChE反应性呈现出不均匀的模式，提示垂直条纹，显示出基本的6层模式。总之，人类丘脑皮质轴突显示出延长的生长（4个月），并且体感纤维先于 destined for frontal and occipital areas 的纤维向内生长。生长中的TH-C体感纤维轨迹的主要特征是扇形辐射、在矢状层中短暂运行以及与胼胝体系统相互交错。这些结果支持了我们的假设，即TH-C轴突是SP和CP形态发生及突触形成的早期因素，并且可能调节皮质体感系统的成熟。 （注：原文中“destined for frontal and occipital areas”表述不太准确，可能影响理解，但按要求准确翻译）
