实验室 | 基础医学院神经生物学系孙琳琳实验室

    北京大学基础医学院主要从事生物医学领域的基础及应用基础研究，拥有雄厚的科学研究综合实力以及一批具备国际先进水平的科研基地和实验技术平台。接下来基础研会将为大家依次介绍北医基础医学院各大实验室，让大家对学院的科研状况能有更为深入的了解。本期将进行基础医学院神经生物学系实验室推送，一起走进孙琳琳实验室！

    药物成瘾实验室的主要研究内容是采用行为药理学、分子生物学、电生理学、形态学等方法探索物质成瘾的神经生物学机制及防治的手段。现有3名教职人员，5名硕/博士研究生。

导师简介

孙琳琳：博士，副研究员，博士生导师。2008年入读北京大学基础医学院八年制。2013年于北京大学神经科学研究所获理学博士学位。曾先后于罗格斯大学，纽约大学，哥伦比亚大学作博士后研究，2021年归国于北京大学基础医学院神经生物学系任教。长期从事药物成瘾记忆及认知障碍，神经病理痛的外周及中枢机制, 以及孤独症神经机制相关的工作，以第一作者/通讯作者在Advanced Science, Nature Communications等国内外高水平期刊发表研究论文多篇。

研究方向

1. 药物成瘾记忆形成、消退和唤起过程中的神经元突触可塑性及其分子机制。

2. 慢性神经病理痛发生发展的外周及中枢机制。

3. 孤独症的本体感觉异常及认知障碍的神经机制。

科研队伍与人才培养

1、科研团队

本实验室共有教职工3名，三年制硕士生3名，五年博士生1名，四年博士生1名。另外2名老师为：

李亦婧：博士，副教授，硕士生导师。2009年于北京大学神经科学研究所获理学博士学位，同年留校任教。于2017-2018年至匹兹堡大学神经科学系进行交流访问。主要从事药物成瘾的神经生物学机制研究，以第一作者身份和参与作者身份发表SCI论文20余篇，先后主持国家自然科学基金面上项目，青年项目等多项科研项目。曾获得第六届全国医学（医药）院校青年教师教学基本功比赛一等奖第一名；北京高校第九届青年教师教学基本功比赛一等奖；首届全国基础医学青年教师讲课比赛特等奖；北京大学优秀教师；中华医学科技奖三等奖（第四完成人）等多项奖励。

姚云：博士，主管技师。2020年毕业于清华大学医学院，获生物医学工程工学博士学位。长期从事于神经科学研究，关注与情绪和动机相关的神经环路。在校期间获研究生国家奖学金，北京市类脑中心优秀博士生奖学金、清华大学优秀学生干部、清华大学优秀共青团员等荣誉。2020年入职于北京大学基础医学院神经生物学系。以第一作者在Cell Reports、Neuroscience Bulletin期刊发表科研论文2篇。

2、培养模式

学生经过对科研文献的充分研读，与导师一起商讨并确立科研方案。随后，学生可根据自己的科研进展和计划，安排每日的科研工作，包括文献学习和实验操作等。每周五举行全组成员的讨论会，学生汇报课题进展或最新的科研文献。导师和全体学生会一起评述本领域的科研进展，深入讨论课题思路及新技术，开阔视野，集思广益，及时解决课题中遇到的问题。

3、实验室氛围

    实验室的氛围融洽，成员之间乐于互相帮助支持。有丰富的技术储备，擅长进行电生理学、光遗传学、形态学、分子生物学及行为学实验。导师和学生沟通充分，能够及时发现和解决各类问题。已毕业研究生均获得过优秀的荣誉，有较好的就业岗位及科研出路。多数毕业生仍继续在国内外各大高校、研究所从事教学和科研工作。

代表性论文

1) Li, Y. #, Guo, X. #, Sun, L. #, Xiao, J. #, Su, S. #, Du, S. #, Li, Z., Wu, S., Liu, W., Mo, K., Xia, S., Chang, Y., Denis, D., Tao, YX. (2020) " N6-methyladenosine demethylase FTO contributes to neuropathic pain by stabilizing G9a expression in primary sensory neurons. " Advanced Science, 375(1799): 234. # co-first author. 

2) Chen, C. #, Zhang, J. #, Sun, L. #, Y. Zhang, W. Gan, P. Tang, G. Yang. (2019) " Long-term imaging of dorsal root ganglia in awake behaving mice." Nature Communications 10(1):3087. # co-first author.

3) Sun, L., Zhou, H., Cichon, J., Yang, G. (2019) "Experience and sleep-dependent synaptic plasticity: from structure to activity. " Philosophical Transactions B 375(1799): 20190234.

4) Sun, L. #, Gu, X. #, Z. Pan, X. Guo, J. Liu, F. E. Atianjoh, S. Wu, K. Mo, B. Xu, L. Liang, A. Bekker and Y. X. Tao. (2019) "Contribution of DNMT1 to neuropathic pain genesis partially through epigenetically repressing Kcna2 in primary afferent neurons." The Journal of Neuroscience 39(33): 6595– 6607. # co-first author. 

5) Li YJ, Ping XJ, Qi C, Shen F, Sun, L, Sun XW, Ge FF, Xing GG, Cui CL. (2017) Re-exposure to morphine-associated context facilitated long-term potentiation in the vSUB-NAc glutamatergic pathway via GluN2B-containing receptor activation. Addiction Biology 22(2):435-445.

6) Sun, L. #, J. Y. Zhao#, X. Gu#, L. Liang, S. Wu, K. Mo, J. Feng, W. Guo, J. Zhang, A. Bekker, X. Zhao, E. J. Nestler and Y. X. Tao. (2017). "Nerve injury-induced epigenetic silencing of opioid receptors controlled by DNMT3a in primary afferent neurons." Pain 158(6): 1153-1165. # co-first author.

7) Sun, L., B. M. Lutz and Y. X. Tao. (2016) "The CRISPR/Cas9 system for gene editing and its potential application in pain research." Translational Perioperative and Pain Medicine 1(3): 22-33. (Review)

8) Sun, L., B. M. Lutz and Y. X. Tao. (2016) "Contribution of Spinal Cord mTORC1 to Chronic Opioid Tolerance and Hyperalgesia." Book: Neuropathology of Drug Addictions and Substance Misuse (Vol. 3, pp. 482-489). Publisher: Elsevier Inc.

9) Li YJ#, Ping XJ#, Yu P, Liang J, Shen F, Han JS, Cui CL. (2016) “Over-expression of the GluN2B subunit in the forebrain facilitates the acquisition of morphine-related positive and aversive memory in rats.” Behavioral Brain Research.311: 416–424. # co-first author. 

10) Li, Z. #, Gu, X. #, Sun, L. #, S. Wu, L. Liang, J. Cao, B. M. Lutz, A. Bekker, W. Zhang and Y. X. Tao. (2015) "Dorsal root ganglion myeloid zinc finger protein 1 contributes to neuropathic pain after peripheral nerve trauma." Pain 156(4): 711-721. # co-first authors

11) Li YJ#, Zuo YF, Yu P, Ping XJ, Cui CL. (2015) "Role of basolateral amygdala dopamine D2 receptors in impulsive choice in acute cocaine-treated rats. " Behavioral Brain Research, 287:187-195.

12) Sun, L. #, Hu, L. #, Li, Y. # and Cui, C. (2013) "Mesoaccumbens dopamine signaling alteration underlies behavioral transition from tolerance to sensitization to morphine rewarding properties during morphine withdrawal." Brain Structure and Function 219(5): 1755-1771. # co-first author.

13) Li YJ，Zhong F，Yu P，Han JS，Cui CL*，Wu LZ*. (2011) "Electroacupuncture treatment normalized sleep disturbance in morphine withdrawal rats. " Evidence-Based Complementary and Alternative Medicine 0101：361054~361054.

14)  Cichon, J., J. Magrane, E. Shtridler, C. Chen, Sun. L, G. Yang and W. B. Gan. (2020) "Imaging neuronal activity in the central and peripheral nervous systems using new Thy1.2-GCaMP6 transgenic mouse lines." Journal of Neuroscience Methods 334: 108535.

15)  Griffiths, K. K., A. Wang, L. Wang, M. Tracey, G. Kleiner, C. M. Quinzii, Sun. L, G. Yang, J. F. Perez-Zoghbi, P. Licznerski, M. Yang, E. A. Jonas and R. J. Levy. (2020) "Inefficient thermogenic mitochondrial respiration due to futile proton leak in a mouse model of fragile X syndrome." The FASEB Journal 10.1096/fj.202000283RR.

16)  Ruan, C., Sun, L., Kroshilina, A., Beckers, L., De Jager, P., Bradshaw, E., Hasson, L., Yang, G., Elyaman, W. (2020) "A Novel Tmem119-tdTomato Reporter Mouse Model for Studying Microglia in the Central Nervous System. "Brain Behavior and Immunity 83(180)-191.

17)  Mao, Q., S. Wu, X. Gu, S. Du, K. Mo, Sun, L., J. Cao, A. Bekker, L. Chen and Y. X. Tao. (2019) "DNMT3a-triggered downregulation of K2p 1.1 gene in primary sensory neurons contributes to paclitaxel-induced neuropathic pain." International Journal of Cancer 145(8):2122-34.

18)  Sun, X., Wang, N., Wang, X., Sun, L., Li, Y., Cui, C. (2019) "AMPA Receptor in Ventromedial Prefrontal Cortex Plays Different Roles in the Recent and Remote Retrieval of Morphine-Associated Memory. " Neurochemical Research 44(8):1939-1949.

19)  Cichon, J., Sun, L. and Yang, G. (2018) "Spared Nerve Injury Model of Neuropathic Pain in Mice. " Bio-protocol 8(6): e2777.

20)  Wang, N., F. Ge, C. Cui, Y. Li, Sun, L. Sun, X. Wang, S. Liu, H. Zhang, Y. Liu, M. Jia and M. Yang. (2018) "Role of Glutamatergic Projections from the Ventral CA1 to Infralimbic Cortex in Context-Induced Reinstatement of Heroin Seeking." Neuropsychopharmacology 43(6):1373-1384. doi: 10.1038/npp.2017.279. Epub 2017 Nov 14.

21)  Zhao, J. Y., L. Liang, X. Gu, Z. Li, S. Wu, L. Sun, F. E. Atianjoh, J. Feng, K. Mo, S. Jia, B. M. Lutz, A. Bekker, E. J. Nestler and Y. X. Tao. (2017) "DNA methyltransferase DNMT3a contributes to neuropathic pain by repressing Kcna2 in primary afferent neurons." Nature Communications 8: 14712. 

22)  Ge FF #, Wang N, Cui CL*, Li YJ, Liu Y, Ma YY, Liu SL, Zhang HL, Sun XW. (2017) "Glutamatergic projections from the entorhinal cortex to dorsal dentate gyrus mediate context-Induced reinstatement of heroin seeking. " Neuropsychopharmacology 42(9):1860-18.

23)  Shen F#, Wang XW#, Ge FF, Li YJ, Cui CL. (2016) "Essential role of the NO signaling pathway in the hippocampal CA1 in morphine-associated memory depends on glutaminergic receptors. " Neuropharmacology 102:216-228.

24)  Xu, J. T., L. Sun, B. M. Lutz, A. Bekker and Y. X. Tao. (2016) "Intrathecal rapamycin attenuates morphine-induced analgesic tolerance and hyperalgesia in rats with neuropathic pain." Translational Perioperative and Pain Medicine 2(2): 27-34.

25)  Li, Y. J., X. J. Ping, C. Qi, F. Shen, L. L. Sun, X. W. Sun, F. F. Ge, G. G. Xing and C. L. Cui. (2015) "Re-exposure to morphine-associated context facilitated long-term potentiation in the vSUB-NAc glutamatergic pathway via GluN2B-containing receptor activation." Addiction Biology 22(2): 435-445.

26)  Lv, X. F., L. L. Sun, C. L. Cui and J. S. Han. (2015) "NAc Shell Arc/Arg3.1 Protein Mediates Reconsolidation of Morphine CPP by Increased GluR1 Cell Surface Expression: Activation of ERK-Coupled CREB is Required." International Journal of Neuropsychopharmacology 18(9): pyv030. Published online 2015 Apr 15. doi: 10.1093/ijnp/pyv030

27)  Qi C#, Wang XJ#, Ge FF, Li YJ, Shen F, Wang JK, Cui CL. (2015) "mGluR5 in the nucleus accumbens shell regulates morphine-associated contextual memory through reactive oxygen species signaling. " Addiction Biology 2015, 20(5):927-940.

28)  Shen F#, Wang N, Qi C, Li YJ, Cui CL. (2014) "The NO/sGC/PKG signaling pathway in the NAc shell is necessary for the acquisition of morphine-induced place preference. "Behavior Neuroscience 128(4):446-459.

29)  Shen F#, Li YJ, Shou XJ, Cui CL. (2012) "Role of the NO/sGC/PKG signaling pathway of hippocampal CA1 in morphine-induced reward memory. "Neurobiology of Learning and Memory (98): 130–138.

30)  Xu Y#, Lv XF, Cui CL*, Ge FF, Li YJ, Zhang HL. (2012) "Essential role of NR2B-containing NMDA receptor–ERK pathway in nucleus accumbens shell in morphine-associated contextual memory. "Brain Research Bulletin (89): 22– 30.

31)  Liang J#, Ma SS#, Li YJ, Ping XJ, Hu L, Cui CL. (2012) "Dynamic changes of tyrosine hydroxylase and dopamine concentrations in the ventral tegmental area-nucleus accumbens projection during the expression of morphine-induced conditioned place preference in rats. " Neurochemical Research 37(7):1482-1489.

32)  Ping XJ#, Ma YY#, Li YJ, Qi C, Sun XW, Lv XF, Cui CL. (2012) "Essential role of protein kinase C in morphine-induced rewarding memory. " Neuropharmacology 62(2):959-966.

33)  Wang GB#, Wu LZ, Yu Peng, Li YJ, Ping XJ, Cui CL. (2011) "Multiple 100 Hz electroacupuncture treatments produced cumulative effect on the suppression of morphine withdrawal syndrome: Central preprodynorphin mRNA and p-CREB implicated. " Peptides 32(4):713-721.

34)  Liang J#, Ping XJ, Li YJ, Ma YY, Wu LZ, Han JS, Cui CL. (2010) "Morphine-induced conditioned place preference in rats is inhibited by electroacupuncture at 2 Hz: role of enkephalin in the nucleus accumbens. " Neuropharmacology 58(1):233-240.

35)  Hu, L, Chu NN, Sun LL, Zhang R, Han JS and Cui CL. (2009) "Electroacupuncture treatment reverses morphine-induced physiological changes in dopaminergic neurons within the ventral tegmental area." Addiction Biology 14(4): 431-437.

联系方式

孙琳琳

实验室地址：北京大学医学部中心楼10层1004房间

Email：linlin.sun@pku.edu.cn

电话：010-82805866

图文 | 孙琳琳实验室

编辑 | 林思梅

审核 | 赵惠聆 高浩萌