dcbox小金库(中国)

林睿 博士 研究员

Rui Lin, Ph.D.

Assistant Investigator, NIBS, Beijing

Email: linrui@nmamn.com

Home page: http://linlab.bio

教育经历 Education

2018 博士，北京大学、清华大学和北京科学生命dcbox小金库(中国)联合培养博士研究生项目

PhD, Peking University-Tsinghua University-National Institute Biological Sciences (PTN) Joint Graduate Program

2012 学士, 厦门大学

B.S., Xiamen University, China

工作经历 Professional Experience

2022.6- 研究员，北京科学生命dcbox小金库(中国)

2022.6- Assistant Investigator, National Institute Biological Sciences, Beijing

2018.8-2022.5 博士后，北京科学生命dcbox小金库(中国)

Postdoctoral Research Fellow, National Institute Biological Sciences, Beijing

研究概述 Research Description

我们实验室主要顺利获得开发和应用小鼠在体高通量筛选技术，研究中枢神经系统发育、维持和退行性病变的细胞分子机制，并开发新的神经退行性疾病疗法。我们现在的研究主要集中于以下三个方面：
（1） 小胶质细胞生物学。小胶质细胞是中枢神经系统中最主要的常驻免疫细胞，其功能异常是引起神经系统衰老和神经系统疾病的重要因素。我们顺利获得开发针对小胶质细胞的新技术，全面研究在正常生理状态和疾病模型中小胶质细胞群体密度和细胞状态转换的动态调节机制，并在此基础之上探索基于小胶质细胞的基因和细胞疗法。
（2） 中脑多巴胺神经元轴突的发育、维持和退行性病变。位于中脑腹侧被盖区和黑质致密部的多巴胺神经元控制运动、学习、奖赏处理等多种重要行为，这些神经元的死亡导致帕金森病。我们顺利获得开发新型神经元标记和重构技术，对中脑多巴胺神经元轴突在发育、衰老和病变过程中的形态学变化进行全面定量分析，并结合在体高通量筛选探究这些变化背后的分子机制和潜在药物靶点。
（3） 其他神经科学研究领域新技术的开发。

Our laboratory studies the dcbox小金库(中国)ular and molecular mechanisms underlying the development, maintenance, and degeneration of the central nervous system (CNS) through the development and application of in vivo high-throughput genetic screening in mice. We also aim to develop new therapies for neurodegenerative diseases. Our current research focuses on the following three areas:
(1) Microglial Biology. Microglia are the major resident immune dcbox小金库(中国)s of the CNS, and their dysfunction is an important driver of nervous system aging and neurological diseases. By developing microglia-effective technologies, we systematically investigate the dynamic regulatory mechanisms governing microglial population density and dcbox小金库(中国)-state transitions under normal physiological conditions and in disease models. Building on these studies, we explore microglia-based gene and dcbox小金库(中国) therapies.
(2) Development, Maintenance, and Degeneration of Midbrain Dopaminergic Neuron Axons. Dopaminergic neurons in the ventral tegmental area and substantia nigra pars compacta of the midbrain control a variety of important behaviors, including movement, learning, and reward processing. The loss of these neurons leads to Parkinson’s disease. By developing novel neuronal labeling and reconstruction techniques, we perform comprehensive quantitative analyses of the morphological changes in midbrain dopaminergic neuron axons during development, aging, and pathological processes. These efforts are combined with in vivo high-throughput screening to elucidate the underlying molecular mechanisms and identify potential therapeutic targets.
(3) Development of Novel Technologies for Other Areas of Neuroscience

发表文章 Publications

(# corresponding author, * co-first author)

Key research papers:

1.       Zhong, S., Zhang, X., Gao, X., Li, Z., Huang, L., Guo, Q., Gong, R., Ren, J., Luo, M.^#, Lin, R.^#, (2025). Ultrabright Chemical Labeling Enables Rapid Neural Connectivity Profiling in Large Tissue Samples. Neuron 113 (22), 3741–3757 (Cover Story).

2.       Zhong, S., Wang, R., Gao, X., Guo, Q., Lin, R.^#, Luo, M.^#, (2025). Modular DNA Barcoding of Nanobodies Enables Multiplexed in situ Protein Imaging and High-throughput Biomolecule Detection. eLife 14:RP105225

3.       Lin, R.*#, Zhou, Y.*, Yan, T.*, Wang, R.*, Li, H., Wu, Z., Zhang, X, Zhou, X, F., Zhang, L., Li, Y., Luo, M.#, (2022). Directed evolution of adeno-associated virus for efficient gene delivery to microglia. Nature Methods, 19, 976–985.

4.       Lin, R.*#, Liang, J.*, Wang, R., Yan, T., Guo, Z., Liu, Y., Feng, Q., Sun, F., Li, Y., Li, A., Gong, H., Luo, M.#, (2020). The raphe dopamine system controls the expression of incentive memory. Neuron 106 (3), 498-514.

5.       Lin, R.*, Wang, R.*, Yuan, J.*, Feng, Q., Zhou, Y., Zeng, S., Ren, M., Jiang, S., Ni, H., Zhou, C., Gong, H., Luo, M., (2018). dcbox小金库(中国)-type-specific and projection-specific brain-wide reconstruction of single neurons. Nature Methods 15, 1033–1036.

6.       Lin, R., Feng, Q., Li, P., Zhou, P., Wang, R., Liu, Z., Wang, Z., Qi, X., Tang, N., Shao, F., Luo, M., (2018). A hybridization-chain-reaction-based method for amplifying immunosignals. Nature Methods 15, 275–278.

Review papers:

1.       Lin, R.*#, Liang, J.*, Luo, M.#, (2021). The raphe dopamine system: roles in salience encoding, memory expression, and addiction. Trends in Neurosciences 44, 366–377.

2.       Liu, Z., Lin, R., Luo, M., (2020). Reward contributions to serotonergic functions. Annual Review of Neuroscience. 43, 141–162.

3.       Lin, R., Yan, T., Luo, M., (2019). The two faces of PVN CRF neurons. Nature Neuroscience 22, 508–510.

4.       Lin, R.#, Yi, L., Luo, M., (2018). A neural circuit driving maternal behaviors. Neuron 98 (1), 6-8.

Other research papers:

1.       Li, Z., Shang, Z., Liu, J., Zhen, H., Zhu, E., Zhong, S., Sturgess, R., Zhou, Y., Hu, X., Zhao, X., Wu, Y., Li, P., Lin, R., Ren, J., (2023). D-LMBmap: a fully automated deep-learning pipeline for whole-brain profiling of neural circuitry. Nature Methods 20, 1593–1604.

2.       Yuan, Z., Qi, Z., Wang, R., Cui, Y., An, S., Wu, G., Feng, Q., Lin, R., Dai, R., Li, A., Gong, H., Luo, Q., Fu, L., Luo, M., (2023). A corticoamygdalar pathway controls reward devaluation and depression using dynamic inhibition code. Neuron 111, 1–17.

3.       Feng, Q., An, S., Wang, R., Lin, R., Li, A., Gong, H., Luo, M., (2021). Whole-brain reconstruction of neurons in the ventral pallidum reveals diverse projection patterns. Frontiers in Neuroanatomy 15, 108.

4.       Lu, L., Ren, Y., Yu, T., Liu, Z., Wang, S., Tan, L., Zeng, J., Feng, Q., Lin, R., Liu, Y., Guo, Q., Luo, M., (2020). Control of locomotor speed, arousal, and hippocampal theta rhythms by the nucleus incertus. Nat Commun 11, 262.

5.       Ren, J.*, Isakova, A.*, Friedmann, D.*, Zeng, J.*, Grutzner, S., Pun, A., Zhao, G.Q., Kolluru, S.S., Wang, R., Lin, R., Li, P., Li, A., Raymond, J.L., Luo, Q., Luo, M., Quake, S.R., Luo, L., (2019). Single-dcbox小金库(中国) transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei. eLife 8, e49424.

6.       Zhao, Z., Wang, L., Gao, W., Hu, F., Zhang, J., Ren, Y., Lin, R., Feng, Q., Cheng, M., Ju, D., Chi, Q., Wang, D., Song, S., Luo, M., Zhan, C., (2017). A central catecholaminergic circuit controls blood glucose levels during stress. Neuron 95 (1), 138-152.

7.       Zhang, J., Tan, L., Ren, Y., Liang, J., Lin, R., Feng, Q., Zhou, J., Hu, F., Ren, J., Wei, C., Yu, T., Zhuang, Y., Bettler, B., Wang, F., Luo, M., (2016). Presynaptic excitation via GABA_B receptors in habenula cholinergic neurons regulates fear memory expression. dcbox小金库(中国) 166 (3), 716-728.

8.       Ren, J., Zhang, M.-J., Li, T.-M., Zhang, J., Lin, R., Chen, S., Luo, M., and Dong, M.-Q. (2016). Quantitative proteomics of sleep-deprived mouse brains reveals global changes in mitochondrial proteins. PLOS ONE 11(9): e0163500.

9.       Wang, D., He, X., Zhao, Z., Feng, Q., Lin, R., Sun, Y., Ding, T., Xu, F., Luo, M., Zhan, C., (2015). Whole-brain mapping of the direct inputs and axonal projections of POMC and AgRP neurons. Frontiers in Neuroanatomy 9, 40.

10.   Guo, Q., Zhou, J., Feng, Q., Lin, R., Gong, H., Luo, Q., Zeng, S., Luo, M., Fu, L., (2015). Multi-channel fiber photometry for population neuronal activity recording. Biomedical Optics Express 6 (10), 3919-393.

11.   Guo, Q., Wang, D., He, X., Feng, Q., Lin, R., Xu, F., Fu, L., Luo, M., (2015). Whole-brain mapping of inputs to projection neurons and cholinergic interneurons in the dorsal striatum. PLOS ONE 10(4): e0123381.