Hartley Nolan D, Krol Alexandra, Choi Soonwook, Rome Nita, Levandowski Kirsten, Pasqualoni Samuel, Jones Carter, Tian Jiawen, Lee Sihak, Lee Husang, Kast Ryan, Feng Guoping, Fu Zhanyan
Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA; Yang Tan Collective and McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Yang Tan Collective and McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cell Rep. 2024 Dec 24;43(12):115037. doi: 10.1016/j.celrep.2024.115037. Epub 2024 Dec 3.
The thalamic reticular nucleus (TRN), the major inhibitory source of the thalamus, plays essential roles in sensory processing, attention, and cognition. However, our understanding of how TRN circuitry contributes to these diverse functions remains limited, largely due to the lack of genetic tools for selectively targeting TRN neurons with discrete structural and physiological properties. Here, we develop Cre mouse lines targeting two genetically segregated populations of TRN neurons that engage first-order (FO) and higher-order (HO) thalamic nuclei, respectively. In addition to substantially distinct electrophysiological properties, these TRN subnetworks are further distinguished by biases in top-down cortical and bottom-up thalamic inputs, along with significant differences in brain-wide synaptic convergence. Furthermore, we demonstrate that dysfunction of each subnetwork results in distinct cortical electroencephalogram (EEG) and sensory processing deficits commonly observed in neuropsychiatric disorders, underscoring the potential involvement of TRN subnetworks in the pathophysiology of these conditions.
丘脑网状核（TRN）是丘脑的主要抑制性来源，在感觉处理、注意力和认知中发挥着重要作用。然而，我们对TRN神经回路如何促成这些多样功能的理解仍然有限，这主要是由于缺乏用于选择性靶向具有离散结构和生理特性的TRN神经元的基因工具。在这里，我们开发了针对两个遗传上分离的TRN神经元群体的Cre小鼠品系，这两个群体分别与一级（FO）和高级（HO）丘脑核发生联系。除了具有明显不同的电生理特性外，这些TRN子网络还通过自上而下的皮质输入和自下而上的丘脑输入偏向进一步区分，同时在全脑突触汇聚方面存在显著差异。此外，我们证明每个子网络的功能障碍会导致在神经精神疾病中常见的不同皮质脑电图（EEG）和感觉处理缺陷，这突出了TRN子网络在这些病症病理生理学中的潜在参与。
