Distinct structural and functional connectivity of genetically segregated thalamoreticular subnetworks
Nolan D. Hartley,
Alexandra Krol,
Soonwook Choi,
Nita Rome,
Kirsten Levandowski,
Samuel Pasqualoni,
Carter Jones,
Jiawen Tian,
Sihak Lee,
Husang Lee,
Ryan Kast,
Guoping Feng,
Zhanyan Fu
Affiliations
Nolan D. Hartley
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
Alexandra Krol
Yang Tan Collective and McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Soonwook Choi
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
Nita Rome
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
Kirsten Levandowski
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
Samuel Pasqualoni
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
Carter Jones
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
Jiawen Tian
Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA
Sihak Lee
Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA
Husang Lee
Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA
Ryan Kast
Yang Tan Collective and McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Guoping Feng
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; Corresponding author
Zhanyan Fu
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; Corresponding author
Summary: 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.
