Multimodal Analysis of Cell Types in a Hypothalamic Node Controlling Social Behavior

控制社会行为的下丘脑节点细胞类型的多模态分析

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作者:Dong-Wook Kim, Zizhen Yao, Lucas T Graybuck, Tae Kyung Kim, Thuc Nghi Nguyen, Kimberly A Smith, Olivia Fong, Lynn Yi, Noushin Koulena, Nico Pierson, Sheel Shah, Liching Lo, Allan-Hermann Pool, Yuki Oka, Lior Pachter, Long Cai, Bosiljka Tasic, Hongkui Zeng, David J Anderson

Abstract

The ventrolateral subdivision of the ventromedial hypothalamus (VMHvl) contains ∼4,000 neurons that project to multiple targets and control innate social behaviors including aggression and mounting. However, the number of cell types in VMHvl and their relationship to connectivity and behavioral function are unknown. We performed single-cell RNA sequencing using two independent platforms-SMART-seq (∼4,500 neurons) and 10x (∼78,000 neurons)-and investigated correspondence between transcriptomic identity and axonal projections or behavioral activation, respectively. Canonical correlation analysis (CCA) identified 17 transcriptomic types (T-types), including several sexually dimorphic clusters, the majority of which were validated by seqFISH. Immediate early gene analysis identified T-types exhibiting preferential responses to intruder males versus females but only rare examples of behavior-specific activation. Unexpectedly, many VMHvl T-types comprise a mixed population of neurons with different projection target preferences. Overall our analysis revealed that, surprisingly, few VMHvl T-types exhibit a clear correspondence with behavior-specific activation and connectivity.

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