PT  - JOURNAL ARTICLE
AU  - Hao-Shan Chen
AU  - Xiao-Long Zhang
AU  - Rong-Rong Yang
AU  - Guang-Ling Wang
AU  - Xin-Yue Zhu
AU  - Yuan-Fang Xu
AU  - Dan-Yang Wang
AU  - Na Zhang
AU  - Shou Qiu
AU  - Li-Jie Zhan
AU  - Zhi-Ming Shen
AU  - Xiao-Hong Xu
AU  - Gang Long
AU  - Chun Xu
TI  - An intein-split transactivator for intersectional neural imaging and optogenetic manipulation
AID  - 10.1101/2021.04.05.438407
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.04.05.438407
4099  - http://biorxiv.org/content/early/2021/04/06/2021.04.05.438407.short
4100  - http://biorxiv.org/content/early/2021/04/06/2021.04.05.438407.full
AB  - The complexity of brain circuitry is manifested by numerous cell types based on genetic marker, location and neural connectivity. Cell-type specific recording and manipulation is essential to disentangle causal neural mechanisms in physiology and behavior; however, many current approaches are largely limited by number of intersectional features, incompatibility of common effectors and insufficient gene expression. To tackle these limitations, we devise an intein-based intersectional synthesis of transactivator (IBIST) to selectively control gene expression of common effectors in specific cell types defined by a combination of multiple features. We validate the specificity and sufficiency of IBIST to control common effectors including fluorophores, optogenetic opsins and Ca2+ indicators in various intersectional conditions in vivo. Using IBIST-based Ca2+ imaging, we show that the IBIST can intersect up to five features, and that hippocampal cells tune differently to distinct emotional valences depending on the pattern of projection targets. Collectively, the IBIST multiplexes the capability to intersect cell-type features and is compatible with common effectors to effectively control gene expression, monitor and manipulate neural activities.Competing Interest StatementThe authors have declared no competing interest.