Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
Brain Struct Funct. 2022 Jun;227(5):1673-1682. doi: 10.1007/s00429-022-02463-4. Epub 2022 Feb 11.
Maternal injection of H-thymidine ([H]dT) during gestation in non-human primates (NHPs) has been used to determine the time of neurogenesis for various brain areas, including the lateral geniculate (LGN) and the pulvinar (PUL) nuclei of the caudal thalamus. Here, we examine neurogenesis in the rostral thalamus, with focus on the mediodorsal (MD) and the anterior nuclei (ANT), to determine if neurogenesis of rostral and caudal thalamic nuclei is concurrent or instead temporally staggered. The MacBrainResource (MBR) search function identified archived cases (N = 10) of [H]dT labeled specimens, with injection dates ranging from embryonic day 25 (E25)-E50 and postnatal sacrifice dates. Slides were scanned to create digital images for subsequent analysis using Stereo Investigator software. Labeled neurons were mapped within a contour that encompassed the entire rostral thalamus. These maps were superimposed onto closely corresponding sections from the online BrainMaps macaque atlas to facilitate analysis. Our novel approach uncovered a previously undetected spatial-temporal patterning of neurogenesis in the thalamus. At E30, labeled neurons were located in a compact medial band; at E38-E40, labeling was dense ventrolaterally, and at E43, labeling predominated laterally at rostral levels and was widely distributed at caudal levels. Peak neurogenesis occurs earlier in MD (E30-E43) and ANT (E31-E43) than in LGN (E36-E43) and PUL (E36-E45). Birth-dating of neurons in MD and ANT, two higher order relay nuclei implicated in the pathology of schizophrenia, provides further insight into the critical period of vulnerability during which early developmental perturbation may increase incidence of schizophrenia later in life.
在非人类灵长类动物（NHPs）中，母体在妊娠期间注射 H-胸腺嘧啶核苷（[H]dT），用于确定各种脑区的神经发生时间，包括外侧膝状体（LGN）和丘脑尾侧的丘脑枕（PUL）核。在这里，我们检查了丘脑的前侧，重点是内侧背核（MD）和前核（ANT），以确定前侧和后侧丘脑核的神经发生是否同时发生，还是时间上错开。MacBrainResource（MBR）搜索功能确定了已存档的 [H]dT 标记标本案例（N=10），注射日期范围从胚胎第 25 天（E25）到 E50 以及出生后牺牲日期。通过扫描幻灯片为后续使用 Stereo Investigator 软件进行分析创建数字图像。将标记的神经元映射到包含整个丘脑前侧的轮廓内。将这些图谱叠加到在线 BrainMaps 猕猴图谱上的紧密对应切片上，以方便分析。我们的新方法揭示了丘脑神经发生的以前未检测到的时空模式。在 E30，标记的神经元位于一个紧密的内侧带中；在 E38-E40，标记在腹外侧密集；在 E43，标记在前侧水平主要位于外侧，并在尾侧水平广泛分布。MD（E30-E43）和 ANT（E31-E43）的神经发生峰值早于 LGN（E36-E43）和 PUL（E36-E45）。MD 和 ANT 中的神经元出生日期，这两个与精神分裂症病理有关的更高阶中继核，进一步深入了解易损性的关键时期，在此期间，早期发育干扰可能会增加日后生活中精神分裂症的发病率。
