Schulmann Anton, Feng Ningping, Auluck Pavan K, Mukherjee Arghya, Komal Ruchi, Leng Yan, Gao Claire, Williams Avram Sarah K, Roy Snehashis, Usdin Ted B, Xu Qing, Imamovic Vesna, Patel Yash, Akula Nirmala, Raznahan Armin, Menon Vilas, Roussos Panos, Duncan Laramie, Elkahloun Abdel, Singh Jatinder, Kelly Michael C, Halassa Michael M, Hattar Samer, Penzo Mario A, Marenco Stefano, McMahon Francis J
Human Genetics Branch, NIMH.
Human Brain Collection Core, NIMH.
bioRxiv. 2024 Sep 5:2024.09.03.611112. doi: 10.1101/2024.09.03.611112.
The mediodorsal thalamus (MD) and adjacent midline nuclei are important for cognition and mental illness, but their cellular composition is not well defined. Using single-nucleus and spatial transcriptomics, we identified a conserved excitatory neuron gradient, with distinct spatial mapping of individual clusters. One end of the gradient was expanded in human MD compared to mice, which may be related to the expansion of granular prefrontal cortex in hominids. Moreover, neurons preferentially mapping onto the parvocellular division MD were associated with genetic risk for schizophrenia and bipolar disorder. Midbrain-derived inhibitory interneurons were enriched in human MD and implicated in genetic risk for major depressive disorder.
丘脑背内侧核（MD）和相邻的中线核团对认知和精神疾病很重要，但其细胞组成尚未明确界定。利用单核和空间转录组学，我们确定了一个保守的兴奋性神经元梯度，各个细胞簇具有独特的空间映射。与小鼠相比，人类MD中该梯度的一端有所扩展，这可能与灵长类动物颗粒状前额叶皮质的扩展有关。此外，优先映射到MD小细胞部的神经元与精神分裂症和双相情感障碍的遗传风险相关。中脑来源的抑制性中间神经元在人类MD中富集，并与重度抑郁症的遗传风险有关。
