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Serotonin receptor 2c-expressing cells in the ventral CA1 control attention via innervation of the Edinger–Westphal nucleus


The hippocampus is divided into dorsal and ventral zones along its principal axis. The dorsal hippocampus is critical for learning and memory, yet the basic function of the ventral hippocampus remains elusive. Here we genetically manipulate a subset of excitatory neurons expressing the serotonin receptor 2c (Htr2c) in the ventral hippocampus. Genetically modified virus tracing reveals that these Htr2c cells establish monosynaptic excitatory connections with newly identified neurons in the Edinger–Westphal nucleus (EW), which directly innervate the medial prefrontal cortex. Inactivation of Htr2c cells impairs behavioral performance in a visual-detection task that demands attention, without affecting novel-object recognition, learning, or memory. This attention deficit was recapitulated by inhibition of EW cells and rescued by activation of EW cells or synaptic projections from Htr2c cells onto EW cells. This study uncovers a synaptic pathway for control of attention.

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Fig. 1: Htr2c cells are a novel group of excitatory neurons.
Fig. 2: Htr2c cells directly innervate EW cells.
Fig. 3: Functional synaptic connections between Htr2c and EW cells.
Fig. 4: Inhibition of Htr2c cells impairs attention.
Fig. 5: Htr2c cells are activated in attention.
Fig. 6: Inhibition of EW cells impairs attention.
Fig. 7: Activation of EW cells enhances attention.


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We thank S. Duan at Zhejiang University, Hangzhou, China, for providing GAD1-Cre mice; M.-H. Luo at Wuhan Institute of Virology, Chinese Academy of Sciences, for the construction and generation of rAAV1/2-DIO-TK, rAAV1/2-DIO-TK-GFP, H129ΔTK-mCh, and H129ΔTK-GFP virus particles; and F. Xu at Britton Chance Center for Biomedical Photonics, Chinese Academy of Sciences, for the construction and generation of RV. This work was supported by the National Natural Science Foundation of China (Grants: 31721002 to YL; 91632306 to Y.L.; 51627807 to Y.L.; 81771150, 81761138043, and 91632114 to L.Q.Z.), the National Program for Support of Top-Notch Young Professionals, and Academic Frontier Youth Team of HUST (to L.Q.Z.).

Author information




Y.L., L.Q.Z., and Q.T. conceived and designed the studies and wrote the paper. X.L., W.C., and K.P. carried out synaptic tracing, mutagenesis and virus construction, and behavioral and optogenetic studies. H.L., P.P., and Y.G. performed electrophysiological studies and immunohistochemistry. S.S., Y.C., L.P., H.K.A., and D.L. performed genotyping, PCR, and cell-counting. All authors contributed to the data analysis and presentation in the paper.

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Correspondence to Ling-Qiang Zhu or Youming Lu.

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Supplementary Text and Figures

Supplementary Figures 1–22

Reporting Summary

Supplementary Table 1

5 stages of 5-CSRT task training schedules

Supplementary Video 1

Correct trial

Supplementary Video 2

Incorrect trial

Supplementary Video 3

Premature trial

Supplementary Video 4

Omission trial

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Li, X., Chen, W., Pan, K. et al. Serotonin receptor 2c-expressing cells in the ventral CA1 control attention via innervation of the Edinger–Westphal nucleus. Nat Neurosci 21, 1239–1250 (2018).

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