The thalamic reticular nucleus (TRN), the major source of thalamic inhibition, regulates thalamocortical interactions that are critical for sensory processing, attention and cognition 1 – 5 . TRN dysfunction has been linked to sensory abnormality, attention deficit and sleep disturbance across multiple neurodevelopmental disorders 6 – 9 . However, little is known about the organizational principles that underlie its divergent functions. Here we performed an integrative study linking single-cell molecular and electrophysiological features of the mouse TRN to connectivity and systems-level function. We found that cellular heterogeneity in the TRN is characterized by a transcriptomic gradient of two negatively correlated gene-expression profiles, each containing hundreds of genes. Neurons in the extremes of this transcriptomic gradient express mutually exclusive markers, exhibit core or shell-like anatomical structure and have distinct electrophysiological properties. The two TRN subpopulations make differential connections with the functionally distinct first-order and higher-order thalamic nuclei to form molecularly defined TRN–thalamus subnetworks. Selective perturbation of the two subnetworks in vivo revealed their differential role in regulating sleep. In sum, our study provides a comprehensive atlas of TRN neurons at single-cell resolution and links molecularly defined subnetworks to the functional organization of thalamocortical circuits. A study integrating single-cell RNA-sequencing and electrophysiology data shows that in mouse, the cellular repertoire of the thalamic reticular nucleus is characterized by a transcriptomic gradient defined at its extremes by mutually exclusive expression of Spp1 and Ecel1 , providing insights into the organizational principles underlying the divergent functions of this brain region.

中文翻译：

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丘脑网状核的不同子网络

丘脑网状核 (TRN) 是丘脑抑制的主要来源，它调节对感觉处理、注意力和认知 1 - 5 至关重要的丘脑皮质相互作用。TRN 功能障碍与多种神经发育障碍的感觉异常、注意力缺陷和睡眠障碍有关 6 - 9。然而，人们对其不同职能背后的组织原则知之甚少。在这里，我们进行了一项综合研究，将小鼠 TRN 的单细胞分子和电生理特征与连接性和系统级功能联系起来。我们发现 TRN 中的细胞异质性以两个负相关基因表达谱的转录组梯度为特征，每个基因表达谱包含数百个基因。这种转录组梯度极端的神经元表达相互排斥的标记，表现出核心或壳状解剖结构，并具有不同的电生理特性。这两个 TRN 亚群与功能不同的一阶和高阶丘脑核建立了不同的连接，以形成分子定义的 TRN-丘脑子网络。体内两个子网络的选择性扰动揭示了它们在调节睡眠中的不同作用。总之，我们的研究提供了单细胞分辨率的 TRN 神经元综合图谱，并将分子定义的子网络与丘脑皮质电路的功能组织联系起来。一项整合单细胞 RNA 测序和电生理学数据的研究表明，在小鼠中，