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Distinct transcriptomic cell types and neural circuits of the subiculum and prosubiculum along the dorsal-ventral axis

By Song-Lin Ding, Zizhen Yao, Karla E. Hirokawa, Thuc Nghi Nguyen, Lucas T. Graybuck, Olivia Fong, Phillip Bohn, Kiet Ngo, Kimberly A Smith, Christof Koch, John W. Phillips, Ed S Lein, Julie A. Harris, Bosiljka Tasic, Hongkui Zeng

Posted 15 Dec 2019
bioRxiv DOI: 10.1101/2019.12.14.876516 (published DOI: 10.1016/j.celrep.2020.107648)

Subicular region plays important roles in spatial processing and many cognitive functions and these were mainly attributed to subiculum (Sub) rather than prosubiculum (PS). Using single-cell RNA-sequencing (scRNA-seq) technique we have identified up to 27 distinct transcriptomic clusters/cell types, which were registered to anatomical sub-domains in Sub and PS. Based on reliable molecular markers derived from transcriptomic clustering and in situ hybridization data, the precise boundaries of Sub and PS have been consistently defined along the dorsoventral (DV) axis. Using these borders to evaluate Cre-line specificity and tracer injections, we have found bona fide Sub projections topographically to structures important for spatial processing and navigation. In contrast, PS along DV axis sends its outputs to widespread brain regions crucial for motivation, emotion, reward, stress, anxiety and fear. Brain-wide cell-type specific projections of Sub and PS have also been revealed using specific Cre-lines. These results reveal two molecularly and anatomically distinct circuits centered in Sub and PS, respectively, providing a consistent explanation to historical data and a clearer foundation for future functional studies.

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