Multimodal analysis reveals cellular diversity and divergent circuits of the zona incerta
Abstract
The zona incerta (ZI) plays an important role in diverse behavioral functions and is an emerging clinical target for deep brain stimulation to treat neurological conditions. Despite their importance, the cell type composition of the ZI and the anatomical circuit organization linking specific ZI cell types to brain-wide circuits remain unclear. In this study, we used single-nucleus RNA-sequencing, spatial RNA profiling, ex vivo electrophysiology, and anatomical circuit mapping to generate a multimodal cellular atlas of the ZI and to characterize the brain-wide monosynaptic inputs to specific ZI cell types. We define four genetically distinct populations of ZI GABAergic neurons that display unique spatial distributions, specialized intrinsic electrophysiological properties, divergent efferent projections, and cell-type-dependent synaptic input patterns. Finally, using fiber photometry, we reveal response divergence between distinct ZI cell types in a behavioral assay that centers around approach-avoidance conflict produced by appetitive and innately aversive stimuli. This study thus provides a foundational resource for the design and interpretation of future experiments aimed at understanding the organization and function of the ZI.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (18)
Ryan Kast
Yang Tan Collective, Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT, Massachusetts Institute of Technology
Sean K. Simmons
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard
Nita Rome
Yang Tan Collective, Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT, Massachusetts Institute of Technology
Xian Adiconis
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard
Lisa Melamed
Yang Tan Collective, Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT, Massachusetts Institute of Technology
Kathryn A. McCabe
McGovern Institute for Brain Research, Massachusetts Institute of Technology
Dongqing Wang
Yang Tan Collective, Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT, Massachusetts Institute of Technology
Alexandra Krol
Yang Tan Collective, Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT, Massachusetts Institute of Technology
Magdalena Krubner
Yang Tan Collective, Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT, Massachusetts Institute of Technology
Vincent Prevosto
McGovern Institute for Brain Research, Massachusetts Institute of Technology
Kirsten Levandowski
Yang Tan Collective, Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT, Massachusetts Institute of Technology
Ubadah Sabbagh
Yang Tan Collective, Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT, Massachusetts Institute of Technology
Heather A. Sullivan
McGovern Institute for Brain Research, Massachusetts Institute of Technology
Ian R. Wickersham
McGovern Institute for Brain Research, Massachusetts Institute of Technology
Fan Wang
Joshua Z. Levin
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard
Zhanyan Fu
McGovern Institute for Brain Research, Massachusetts Institute of Technology
Guoping Feng