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伊鸣研究员课题组

 

 

 

   

 

Ming Yi    Ph.D.

Principal Investigator

Laboratory for Cognitive Neuroscience

Neuroscience Research Institute

Peking University

38 Xueyuan Road

Beijing 100083, China

Tel: + 86(0)10 8280 5083 

Email: mingyi@hsc.pku.edu.cn

 

 

Academic experience

 Dr. Yi received his medical degree in Peking University Health Science Center, and Ph.D. training in John O’Keefe (2014 Nobel laureate) group in the Department of Anatomy and Developmental Biology of University College London (UCL). Dr. Yi is currently a principal investigator and leads the Laboratory for Cognitive Neuroscience in Neuroscience Research Institute of Peking University.

 

Research: Hippocampal physiology and function 

The hippocampus plays a pivotal role in multiple physiological processes such as spatial navigation, declarative memory and emotion. Furthermore, the high neuroplastic capacity makes the hippocampus a priority target of various pathological conditions such as Alzheimer’s disease, epilepsy, depression and chronic pain.

 

Yi’s lab focuses on understanding physiology and function of the hippocampal system with combinative application of in vivo and in vitro electrophysiology, behavioral testing, opto- and chemo-genetics and molecular biology.

 

 (1) Neuronal basis of declarative memory

The hippocampus contains place cells and engram cells crucial for spatial navigation and declarative memory, respectively. It is both fascinating and challenging to understand the mechanisms of memory encoding, storage and retrieval, to clarify how these processes deteriorate under pathological conditions, and to “control” these processes. Dr Yi’s early work has provided evidence of how hippocampal place cell networks undergo progressive functional deterioration in a mouse model of Alzheimer’s disease (PNAS. 2008). More recently, Yi’s lab has achieved erasure of specific memory traces from rat neocortices with combined cell labeling and CRISPR-based gene editing techniques (Sci Adv. 2020). Ongoing work is focused on erasing negative affective engrams from specific neuronal populations, which will provide novel intervention options for chronic pain and emotional disturbances such as post-traumatic stress disorder.

 

 (2) Hippocampal circuitry in pain modulation

Pain is a multi-dimensional phenomenon with perceptual, affective, cognitive and social components. Recent clinical and neuroimaging findings have consistently demonstrated an intriguing role of the hippocampus in modulating the transition to chronic pain. But the underlying mechanisms remain elusive. Yi’s lab pioneers in deciphering the hippocampal circuitry in pain modulation (J Neurosci. 2017; Pain. 2018; Cell Rep. 2019). In particular, the neural correlate of spontaneous pain has been one surprisingly poorly understood question in pain research. Using a circuit dynamics-based strategy, Yi’s lab has recently identified a neural pathway (ventral hippocampal CA1-infralimbic cortex, vCA1-IL) that specifically correlates with spontaneous pain behaviour and modulates overall pain progression in rats with peripheral inflammation (Cell Rep. 2019). Current research is focused on clarifying the contribution of specific neuronal subpopulations to various behavioural dimensions in chronic pain, identifying key molecular substrates, and translating to clinical application.

 

 

Representative publications 

 

Sun H, Fu S, Yin X, Sun X, Qi X, Cui K, Wang J, Ma L, Liu FY, Cui S, Liao FF, Wang XH, Yi M, Wan Y. Development of CRISPR-SaCas9 system for projection- and function-specific gene editing in the rat brain. Sci Adv. 2020; 6: eaay6687.

 

Ma L, Yue L, Zhang Y, Wang Y, Han B, Cui S, Liu FY, Wan Y, Yi M. Spontaneous pain disrupts ventral hippocampal CA1-infralimbic cortex connectivity and modulates pain progression in rats with peripheral inflammation. Cell Rep. 2019;29:1579–1593.

 

Ma L, Zhang Y, Yue L, Zhang X, Cui S,  Liu F, Wan Y, Yi M. Anterior cingulate cortex modulates the affective-motivative dimension of hyperosmolality-induced thirst. J Physiol. 2019; 597(18):4851-4860.

 

Jin X, Chen Q, Song Y, Zheng J, Xiao K, Shao S, Fu Z, Yi M, Yang Y, Huang Z. Dopamine D2 receptors regulate the action potential threshold by modulating T-type calcium channels in stellate cells of the medial entorhinal cortex. J Physiol. 2019;597(13):3363-3387.

 

Jiang Y, Shao S, Zhang Y, Zheng J, Chen X, Cui S, Liu FY, Wan Y, Yi M. Neural pathways in medial septal cholinergic modulation of chronic pain: distinct contribution of anterior cingulate cortex and ventral hippocampus. Pain. 2018. 159(8):1550-1561.

 

Peng WW, Xia XL, Yi M, Huang G, Zhang ZG, Iannetti GD, Hu L. Brain oscillations reflecting pain-related behavior in freely moving rats. Pain. 2018. 159(1):106–118.

 

Fan XC, Fu S, Liu FY, Cui S, Yi M, Wan Y. Hypersensitivity of prelimbic cortex neurons contributes to aggravated nociceptive responses in rats with experience of chronic inflammatory pain. Front Mol Neurosci. 2018. 11:85.

 

Zheng J, Jiang YY, Xu LC, Ma LY, Liu FY, Cui S, Cai J, Liao FF, Wan Y, Yi M. Adult hippocampal neurogenesis along the dorsoventral axis contributes differentially to environmental enrichment combined with voluntary exercise in alleviating chronic inflammatory pain in mice. J Neurosci. 2017; 37(15):4145-4157.

 

Liu Y, Lai S, Ma W, Ke W, Zhang C, Liu S, Zhang Y, Pei F, Li S, Yi M, Shu Y, Shang Y, Liang J, Huang Z. CDYL suppresses epileptogenesis in mice through repression of axonal Nav1.6 sodium channel expression. Nat Commun. 2017;8(1):355.

 

Yi M, Zhang H. Nociceptive memory in the brain: cortical mechanisms of chronic pain. J Neurosci. 2011. 31:13343-13345. 

 

Cacucci F *, Yi M *, Wills TJ, Chapman P, O'Keefe J. Place cell firing correlates with memory deficits and amyloid plaque burden in Tg2576 Alzheimer mouse model. Proc

 

Natl Acad Sci U S A. 2008; 105(22): 7863-8.

 

 

Funding

  1. 2020 Key Basic Research Program, CMC
  2. 2019 National Natural Science Foundation (31872774)
  3. 2018 Beijing Natural Science Foundation  (5182013)
  4. 2015 National Basic Research Program of MOST (2015CB554503)
  5. 2014 National Basic Research Program of MOST (2014CB548200)
  6. 2012 National Natural Science Foundation (31200835)

 

 

Teaching

  1.  “Cognitive functions of the brain”, in Advanced Neurobiology
  2. “In vivo electrophysiology and optogenetics”, in Research Methods in Neurobiology
  3. “Advances in hippocampal physiology and function”, in Advances in Neuroscience
  4. “Neurobiology”, in Foundation of Scientific Research

 

 

    博士

 

北京大学百人计划研究员

认知神经科学实验室

 

 

联系方式:

 

地址:北京市海淀区学院路38号北京大学神经科学研究所

邮编:100083

电话:(010) 82805083

E-mail: mingyi@hsc.pku.edu.cn

 

 

学术经历

于北京大学医学部临床医学专业获医学学士学位,英国伦敦大学学院(University College London, UCL)解剖与发育生物学系神经科学专业获哲学博士学位(导师John O’Keefe教授,英国皇家科学院、皇家医学院、美国科学院院士,2014年诺贝尔生理学或医学奖获得者)。现任北京大学神经科学研究所认知神经科学实验室研究员。

 

 

研究方向:海马脑区生理学与功能

海马脑区是最受关注的脑区之一,在空间定位、陈述性记忆、情绪等多种认知过程中发挥重要作用,同时也在阿尔茨海默病、癫痫、抑郁、慢性痛等诸多疾病中受累。

伊鸣实验室联合应用清醒动物在体电生理记录、光/化学遗传学、分子生物学、脑片膜片钳、行为学等多项先进技术,关注海马脑区的生理学与功能。

 

  (1) 陈述性记忆的细胞基础

    海马含有位置细胞和印记细胞,在陈述性记忆的编码中发挥重要作用。伊鸣博士的早期工作揭示了阿尔茨海默病小鼠模型中海马神经网络的电生理特征(PNAS. 2008)。最近,伊鸣实验室将神经元标记技术与基于CRISPR-Cas9系统的基因编辑技术结合应用,实现了通路特异性与功能特异性神经元亚群的基因编辑,进而实现新皮层中特定记忆的精确删除(Sci Adv. 2020)。目前的工作集中于应用基因编辑技术特异性删除负性情绪印记,为创伤后应激综合征、药物成瘾、慢性焦虑、慢性痛等多种以病理性记忆为特征的疾病治疗提供新思路。

2)海马回路与痛觉调控

疼痛是包含感觉、情绪、认知和社会成分的多维度现象。近年来,临床与脑成像研究提示海马回路参与调控疼痛慢性化,但具体机制不清。伊鸣实验室应用自由活动动物多脑区同步电生理记录等多项先进技术,系统研究以海马脑区为核心的神经网络参与痛觉调控的机制(J Neurosci. 2017;Pain. 2018; Cell Rep. 2019)。其中,自发痛的神经生物学机制是疼痛领域备受关注的问题。伊鸣实验室通过行为学、神经网络动力学与遗传学结合的研究策略,发现与炎症痛中自发性痛行为特异性相关的神经通路(腹侧海马CA1-边缘下皮质通路,vCA1-IL)(Cell Rep. 2019)。目前的工作集中于揭示慢性痛不同行为维度的分子、细胞与神经回路基础及临床转化研究。

 

核心技术

自由活动动物在体电生理记录与神经计算

通过手术将微电极阵列埋置在动物特定脑区后,在动物清醒自由活动状态下进行行为学实验,同时记录各脑区的神经元动作电位和神经元群局部场电位。进而通过数学方法分析记录到的电信号频率、幅度、相位等特征,在神经网络层面研究脑功能特征。这项技术可以直接、长期、同步观察清醒动物特定核团神经元活动与行为相关性。

 

/化学遗传学

光遗传学与化学遗传学技术是神经科学前沿技术,通过光脉冲或特定药物精确调控特定脑区特定类型神经元活动模式,进而研究其对行为的影响。

光遗传学技术首先通过转基因技术或病毒转染,使动物特定脑区特定类型神经元或神经回路表达兴奋性或抑制性光敏蛋白,进而通过光纤用激光或LED光脉冲人为地时空特异性控制光敏蛋白传输兴奋性的阳离子流或者抑制性的阴离子流,进而精确控制细胞或神经回路的活动状态。

化学遗传学技术通过转基因技术或病毒转染,使动物特定脑区特定类型神经元表达专门设计的兴奋性或抑制性G蛋白偶联受体,进而局部或系统注射专门设计的激活此受体的药物控制相应细胞或神经回路的活动状态。其操作比光遗传学更简单,作用更持久。

此外,基因编辑、分子生物学、钙成像、脑片膜片钳、动物行为学、高密度脑电等其他先进技术均有应用。

 

代表性论文

 

Sun H, Fu S, Yin X, Sun X, Qi X, Cui K, Wang J, Ma L, Liu FY, Cui S, Liao FF, Wang XH, Yi M, Wan Y. Development of CRISPR-SaCas9 system for projection- and function-specific gene editing in the rat brain. Sci Adv. 2020; 6: eaay6687.

Ma L, Yue L, Zhang Y, Wang Y, Han B, Cui S, Liu FY, Wan Y, Yi M. Spontaneous pain disrupts ventral hippocampal CA1-infralimbic cortex connectivity and modulates pain progression in rats with peripheral inflammation. Cell Rep. 2019;29:1579–1593.

Ma L, Zhang Y, Yue L, Zhang X, Cui S,  Liu F, Wan Y, Yi M. Anterior cingulate cortex modulates the affective-motivative dimension of hyperosmolality-induced thirst. J Physiol. 2019; 597(18):4851-4860.

Jin X, Chen Q, Song Y, Zheng J, Xiao K, Shao S, Fu Z, Yi M, Yang Y, Huang Z. Dopamine D2 receptors regulate the action potential threshold by modulating T-type calcium channels in stellate cells of the medial entorhinal cortex. J Physiol. 2019;597(13):3363-3387.

Jiang Y, Shao S, Zhang Y, Zheng J, Chen X, Cui S, Liu FY, Wan Y, Yi M. Neural pathways in medial septal cholinergic modulation of chronic pain: distinct contribution of anterior cingulate cortex and ventral hippocampus. Pain. 2018. 159(8):1550-1561.

Peng WW, Xia XL, Yi M, Huang G, Zhang ZG, Iannetti GD, Hu L. Brain oscillations reflecting pain-related behavior in freely moving rats. Pain. 2018. 159(1):106–118.

Fan XC, Fu S, Liu FY, Cui S, Yi M, Wan Y. Hypersensitivity of prelimbic cortex neurons contributes to aggravated nociceptive responses in rats with experience of chronic inflammatory pain. Front Mol Neurosci. 2018. 11:85.

Zheng J, Jiang YY, Xu LC, Ma LY, Liu FY, Cui S, Cai J, Liao FF, Wan Y, Yi M. Adult hippocampal neurogenesis along the dorsoventral axis contributes differentially to environmental enrichment combined with voluntary exercise in alleviating chronic inflammatory pain in mice. J Neurosci. 2017; 37(15):4145-4157.

Liu Y, Lai S, Ma W, Ke W, Zhang C, Liu S, Zhang Y, Pei F, Li S, Yi M, Shu Y, Shang Y, Liang J, Huang Z. CDYL suppresses epileptogenesis in mice through repression of axonal Nav1.6 sodium channel expression. Nat Commun. 2017;8(1):355.

Xiao X, Zhao XT, Xu LC, Yue LP, Liu FY, Cai J, Liao FF, Kong JG, Xing GG, Yi M, Wan Y. Shp-1 dephosphorylates TRPV1 in dorsal root ganglion neurons and alleviates CFA-induced inflammatory pain in rats. Pain. 2015; 156(4): 597-608.

Yi M, Zhang H. Nociceptive memory in the brain: cortical mechanisms of chronic pain. J Neurosci. 2011. 31:13343-13345. 

Cacucci F *, Yi M *, Wills TJ, Chapman P, O'Keefe J. Place cell firing correlates with memory deficits and amyloid plaque burden in Tg2576 Alzheimer mouse model. Proc Natl Acad Sci U S A. 2008; 105(22): 7863-8.

 

科研资助与奖励

 

2020年基础加强计划重点基础研究项目

2019年国家自然科学基金(31872774

2019年北京市青年人才托举计划

2018年北京自然科学基金(5182013

2015年国家重点基础研究发展计划(973计划)(2015CB554503

2014973计划青年科学家专题(2014CB548200

2012年国家自然科学基金(31200835

2015年国家科学技术进步奖二等奖(5/10

 

教学

 

本科生课程《科研思维训练》:神经生物学

研究生课程《高级神经生物学》:脑的高级认知功能

研究生课程《神经科学进展》:认知神经科学研究进展

研究生课程《神经生物学实验》:清醒动物在体电生理与光遗传学技术

北京大学医学部教师教学发展中心培训导师

2017年北京大学医学部教学优秀奖

2014年中华医学会医学教育分会第四届医学(医药)院校青年教师教学基本功比赛特等奖,最受学生欢迎奖,最佳教案奖

2013年北京高校第八届青年教师教学基本功比赛一等奖,最受学生欢迎奖,最佳演示奖

2013年北京大学医学部教学优秀奖

2012年北京大学第十二届青年教师教学演示竞赛(医科类)一等奖

2012年北京大学基础医学院第十二届青年教师教学演示竞赛一等奖

 

 

实验室成员