学科带头人 徐林 研究员 博士生导师

　　1963年2月出生，四川泸州市人。中国科学院动物模型与人类疾病机理重点实验室主任，中国科学院昆明动物研究所所学术委员会主任。1985年毕业于四川南充师范学院生物系获学士学位，1989年毕业于中科院昆明动物研究所脑与行为实验室获硕士学位。1994年到英国伦敦大学药学院药理系做访问学者，1995年于爱尔兰三一学院攻读博士，毕业于1998年获得博士学位。1999年入选中国科学院“百人计划”和并获得国家基金委杰出青年基金，先后获得云南省科学技术进步一等奖、973先进个人和谈家桢生命科学创新奖。现任云南大学、中南大学湘雅二医院精神卫生研究所、中国科技大学博士生导师；中国科学院上海神经研究所客座研究员；中国神经科学学会“神经药理学专业委员会”副主任，中国生物物理学会理事，中国生理学会“生理心理学委员会”委员；国家自然科学基金委、国家科技部聘任项目评审专家；10多种国际神经科学SCI杂志的评审专家，《Neural Plasticity》和《Behavioural Brain Research》杂志编辑。

主持/承担973计划、重大新药创制、国家自然科学基金、中国科学院重要创新方向等重大研究项目，在《Nature》, 《Neuron》, 《PNAS》,《JNS》,《JBC》, 《Hippocampus》等杂志上发表SCI论文50余篇。其中1998年发表的Nature论文被Thomas Donaldson(1998)列入了近代记忆研究目录28篇论文之一。目前已申请抗老年痴呆和抗心理应激国内专利4项，抗抑郁新药国际专利2项，治疗精神疾病设备国际专利1项。

 

研究方向

　　本学科组长期围绕神经系统活动的信息加工编码及其与神经、精神疾病间的关系开展理论和应用基础研究。采用离体脑片、麻醉动物和清醒动物电生理技术，结合行为学、神经药理学、分子生物学、生物信息学等多种手段，在学习记忆、药物依赖和精神疾病等方面取得了创新性的研究成果。充分利用云南省丰富多样的生物资源优势，进行抗精神疾病新药筛选和药理药效学研究，逐渐形成具有国际竞争力的学科团队。

　　首次发现应激易化海马突触效能长时程降低(LTD)(Nature, 1997)，其效应依赖于糖皮质激素受体介导的翻译和转录(PNAS, 1998)。发现新颖探索学习逆转海马突触效能长时程增强(LTP)(Nature, 1998)。应激易化海马LTD与应激损伤记忆没有直接联系，而与应激事件记忆有关(Neurosci Res, 2003)。应激增强幼年，但损伤成年、中年、老年动物的记忆能力(J Endocinol, 2003)，却总是易化LTD、损伤LTP，是应激事件记忆的基础(Brain Res, 2004)。应激导致神经细胞信息输出的长时可塑性，应激易化的LTD导致信息输出降低，但LTP对信息输出没有影响(Neurosci Res, 2004)。单独吗啡注射导致LTP，但吗啡注射和应激共同作用导致LTD；同时吗啡和应激共同作用导致强烈的、不消退的毒品寻求行为(J Neurosci, 2004)。光-电刺激恐惧记忆的建立和提取，可级量化地反映在海马LTP/LTD上(Hippocampus, 2005)。应激破坏了海马信息输入和皮层信息输入的整合自稳态(Neuroreport, 2006)。抗抑郁症药物影响海马突触可塑性，降低应激诱导的超声波功率(Eur J Pharmacol, 1997)，逆转了应激对海马-前额叶通路LTP的易化效应(Neuroreport, 2006)。5-HT缺失可导致应激对海马突触可塑性的影响的消失，同时伴随着恐惧记忆和毒品成瘾记忆的持续不消退(PNAS, 2008)。海马神经细胞辣椒素受体具有很好的抗应激效果，可能是一个很好的抗应激、治疗焦虑和抑郁症的新药物靶点(Biol Psychiat, 2008)。

动物模型和研究新技术的建立，也取得了创新性成果：1）发展和完善了多种应激相关的焦虑和抑郁症动物模型；2）建立了吗啡Morris水迷宫的延缓逃避任务，强迫性毒品寻求行为；3）建立了全新的、能同时记录神经信息输入输出的电生理学技术。

 

科研任务（2003-今）

注：括号内为为主持的项目数。

研究团队（2003-今）

 

发表论文（#第一作者，*通讯作者）

2008年发表论文

 

[1] Zuo J, Liu Z, Ouyang X, Liu H, Hao Y, Xu L, Lu XH: Distinct neurobehavioral consequences of prenatal exposure to sulpiride (SUL) and risperidone (RIS) in rats. Prog Neuropsychopharmacol Biol Psychiatry 2008, 32:387-397.

[2] Zhang Z, Gong N, Wang W, Xu L, Xu TL: Bell-shaped D-serine actions on hippocampal long-term depression and spatial memory retrieval. Cereb Cortex 2008, 18:2391-2401.

[3] Zhang LH, Gong N, Fei D, Xu L, Xu TL: Glycine uptake regulates hippocampal network activity via glycine receptor-mediated tonic inhibition. Neuropsychopharmacology 2008, 33:701-711.

[4] Xu L^#*: [Neural plasticity mechanism of depression]. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2008, 33:326-330.

[5] Liu H, Li L, Hao Y, Cao D, Xu L, Rohrbaugh R, Xue Z, Hao W, Shan B, Liu Z: Disrupted white matter integrity in heroin dependence: a controlled study utilizing diffusion tensor imaging. Am J Drug Alcohol Abuse 2008, 34:562-575.

[6] Li HB^#, Mao RR^#, Zhang JC, Yang Y, Cao J, Xu L*: Antistress effect of TRPV1 channel on synaptic plasticity and spatial memory. Biol Psychiatry 2008, 64:286-292.

[7] Gao Y, Han H^#, Xu R, Cao J, Luo J, Xu L^*: Effects of prolonged exposure to context following contextual fear conditioning on synaptic properties in rat hippocampal slices. Neurosci Res 2008, 61:385-389.

[8] Dong Z^#, Zhong W, Tian M, Han H, Mao R, Cao J, Sui N, Xu T, Luo J, Xu L*: Morphine withdrawal affects both delayed-escape behaviour in Morris water maze and hippocampal NR2A/2B expression ratio. Brain Res 2008, 1207:164-173.

[9] Dong Z^#, Han H^#, Cao J, Zhang X, Xu L*: Coincident activity of converging pathways enables simultaneous long-term potentiation and long-term depression in hippocampal CA1 network in vivo. PLoS ONE 2008, 3:e2848.

[10]Dai JX, Han HL^#, Tian M, Cao J, Xiu JB, Song NN, Huang Y, Xu TL, Ding YQ, Xu L*: Enhanced contextual fear memory in central serotonin-deficient mice. Proc Natl Acad Sci U S A 2008, 105:11981-11986.

 

 

2007年发表论文

 

[1] Yang J, Hou C, Ma N, Liu J, Zhang Y, Zhou J, Xu L*, Li L: Enriched environment treatment restores impaired hippocampal synaptic plasticity and cognitive deficits induced by prenatal chronic stress. Neurobiol Learn Mem 2007, 87:257-263.

[2] Ma WP^#, Cao J, Tian M, Cui MH, Han HL, Yang YX, Xu L*: Exposure to chronic constant light impairs spatial memory and influences long-term depression in rats. Neurosci Res 2007, 59:224-230.

[3]Ma N, Li L, Shu N, Liu J, Gong G, He Z, Li Z, Tan L, Stone WS, Zhang Z, et al: White matter abnormalities in first-episode, treatment-naive young adults with major depressive disorder. Am J Psychiatry 2007, 164:823-826.

[4]Li L, Ma N, Li Z, Tan L, Liu J, Gong G, Shu N, He Z, Jiang T, Xu L*: Prefrontal white matter abnormalities in young adult with major depressive disorder: a diffusion tensor imaging study. Brain Res 2007, 1168:124-128.

[5] Duan B, Wu LJ, Yu YQ, Ding Y, Jing L, Xu L*, Chen J, Xu TL: Upregulation of acid-sensing ion channel ASIC1a in spinal dorsal horn neurons contributes to inflammatory pain hypersensitivity. J Neurosci 2007, 27:11139-11148.

[6] Dong Z^#, Cao J, Xu L*: Opiate withdrawal modifies synaptic plasticity in subicular-nucleus accumbens pathway in vivo. Neuroscience 2007, 144:845-854.

 

2006年发表论文

[1] Zhou J, Wang X, Li L, Cao X, Xu L*, Sun Y: Plasma serotonin levels in young violent offenders: Aggressive responding and personality correlates. Prog Neuropsychopharmacol Biol Psychiatry 2006, 30:1435-1441.

[2] Zhong WX, Dong ZF, Tian M, Cao J, Xu L, Luo JH: N-methyl-D-aspartate receptor-dependent long-term potentiation in CA1 region affects synaptic expression of glutamate receptor subunits and associated proteins in the whole hippocampus. Neuroscience 2006, 141:1399-1413.

[3] Zhong W, Dong Z, Tian M, Cao J, Xu T, Xu L, Luo J: Opiate withdrawal induces dynamic expressions of AMPA receptors and its regulatory molecule CaMKIIalpha in hippocampal synapses. Life Sci 2006, 79:861-869.

[4] Yang J, Li W, Liu X, Li Z, Li H, Yang G, Xu L*, Li L: Enriched environment treatment counteracts enhanced addictive and depressive-like behavior induced by prenatal chronic stress. Brain Res 2006, 1125:132-137.

[5] Yang J, Han H, Cui M, Wang L, Cao J, Li L, Xu L*: Acute behavioural stress facilitates long-term depression in temporoammonic-CA1 pathway. Neuroreport 2006, 17:753-757.

[6] Yang J, Han H, Cao J, Li L, Xu L*: Prenatal stress modifies hippocampal synaptic plasticity and spatial learning in young rat offspring. Hippocampus 2006, 16:431-436.

[7] Wang W, Duan B, Xu H, Xu L, Xu TL: Calcium-permeable acid-sensing ion channel is a molecular target of the neurotoxic metal ion lead. J Biol Chem 2006, 281:2497-2505.

[8] Wang MN^#, Dong ZF, Cao J, Xu L*: Repeated morphine treatment influences operant and spatial learning differentially. Neurosci Bull 2006, 22:137-143.

[9] Wang M^#, Yang Y, Dong Z, Cao J, Xu L*: NR2B-containing N-methyl-D-aspartate subtype glutamate receptors regulate the acute stress effect on hippocampal long-term potentiation/long-term depression in vivo. Neuroreport 2006, 17:1343-1346.

[10]Sun N, Li Y, Tian S, Lei Y, Zheng J, Yang J, Sui N, Xu L, Pei G, Wilson FA, et al: Dynamic changes in orbitofrontal neuronal activity in rats during opiate administration and withdrawal. Neuroscience 2006, 138:77-82.

[11]Liu H, Liu Z, Liang M, Hao Y, Tan L, Kuang F, Yi Y, Xu L, Jiang T: Decreased regional homogeneity in schizophrenia: a resting state functional magnetic resonance imaging study. Neuroreport 2006, 17:19-22.

[12]Kessal K, Deschaux O, Chessel A, Xu L, Moreau JL, Garcia R: Fluoxetine reverses stress-induced fimbria-prefrontal long-term potentiation facilitation. Neuroreport 2006, 17:319-322.

[13]Hao Y, Liu Z, Jiang T, Gong G, Liu H, Tan L, Kuang F, Xu L, Yi Y, Zhang Z: White matter integrity of the whole brain is disrupted in first-episode schizophrenia. Neuroreport 2006, 17:23-26.

[14]Dong Z^#, Zhong W, Tian M, Han H, Cao J, Xu T, Luo J, Xu L: Stress evoked by opiate withdrawal facilitates hippocampal LTP in vivo. Hippocampus 2006, 16:1017-1025.

[15]Dong Z^#, Mao R, Han H, Cao J, Xu L*: Morphine withdrawal modifies antinociceptive effects of acute morphine in rats. Biochem Biophys Res Commun 2006, 346:578-582.

[16]Dong Z^#, Han H, Wang M, Xu L, Hao W, Cao J*: Morphine conditioned place preference depends on glucocorticoid receptors in both hippocampus and nucleus accumbens. Hippocampus 2006, 16:809-813.

[17]Cui M^#, Yang Y, Yang J, Zhang J, Han H, Ma W, Li H, Mao R, Xu L, Hao W, Cao J*: Enriched environment experience overcomes the memory deficits and depressive-like behavior induced by early life stress. Neurosci Lett 2006, 404:208-212.

 

2005年发表论文

 

[1] Zhang J, Yang Y, Li H, Cao J, Xu L*: Amplitude/frequency of spontaneous mEPSC correlates to the degree of long-term depression in the CA1 region of the hippocampal slice. Brain Res 2005, 1050:110-117.

[2] Sun X, Zhang J, Li H, Zhang Z, Yang J, Cui M, Zeng B, Xu T, Cao J, Xu L*: Propofol effects on excitatory synaptic efficacy in the CA1 region of the developing hippocampus. Brain Res Dev Brain Res 2005, 157:1-7.

[3] Li Z, Zhou Q, Li L, Mao R, Wang M, Peng W, Dong Z, Xu L, Cao J*: Effects of unconditioned and conditioned aversive stimuli in an intense fear conditioning paradigm on synaptic plasticity in the hippocampal CA1 area in vivo. Hippocampus 2005, 15:815-824.

[4] Li H, Zhang J, Xiong W, Xu T, Cao J, Xu L*: Long-term depression in rat CA1-subicular synapses depends on the G-protein coupled mACh receptors. Neurosci Res 2005, 52:287-294.

[5] Gao J, Duan B, Wang DG, Deng XH, Zhang GY, Xu L, Xu TL: Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death. Neuron 2005, 48:635-646.

 

2004年发表论文

 

[1] Yang Y, ^# Zheng X, Wang Y, Cao J, Dong Z, Cai J, Sui N, Xu L*: Stress enables synaptic depression in CA1 synapses by acute and chronic morphine: possible mechanisms for corticosterone on opiate addiction. J Neurosci 2004, 24:2412-2420.

[2] Xiong W^#, Wei H, Xiang X, Cao J, Dong Z, Wang Y, Xu T, Xu L*: The effect of acute stress on LTP and LTD induction in the hippocampal CA1 region of anesthetized rats at three different ages. Brain Res 2004, 1005:187-192.

[3] Wu LJ, Duan B, Mei YD, Gao J, Chen JG, Zhuo M, Xu L, Wu M, Xu TL: Characterization of acid-sensing ion channels in dorsal horn neurons of rat spinal cord. J Biol Chem 2004, 279:43716-43724.

[4] Gao J, Wu LJ, Xu L, Xu TL: Properties of the proton-evoked currents and their modulation by Ca2+ and Zn2+ in the acutely dissociated hippocampus CA1 neurons. Brain Res 2004, 1017:197-207.

[5] Cao J^#, Chen N, Xu T, Xu L*: Stress-facilitated LTD induces output plasticity through synchronized-spikes and spontaneous unitary discharges in the CA1 region of the hippocampus. Neurosci Res 2004, 49:229-239.

 

2003年前发表论文

 

[1] Wei H, Xiong W, Yang S, Zhou Q, Liang C, Zeng BX, Xu L*: Propofol facilitates the development of long-term depression (LTD) and impairs the maintenance of long-term potentiation (LTP) in the CA1 region of the hippocampus of anesthetized rats. Neurosci Lett 2002, 324:181-184.

[2] Xu L^#, Holscher C, Anwyl R, Rowan MJ: Glucocorticoid receptor and protein/RNA synthesis-dependent mechanisms underlie the control of synaptic plasticity by stress. Proc Natl Acad Sci U S A 1998, 95:3204-3208.

[3] Xu L^#, Anwyl R, Rowan MJ: Spatial exploration induces a persistent reversal of long-term potentiation in rat hippocampus. Nature 1998, 394:891-894.

[4] Rowan MJ, Anwyl R, Xu L: Stress and long-term synaptic depression. Mol Psychiatry 1998, 3:472-474.

[5] Xu L^#, Anwyl R, Rowan MJ: Behavioural stress facilitates the induction of long-term depression in the hippocampus. Nature 1997, 387:497-500.

[6] Xu L^#, Anwyl R, De Vry J, Rowan MJ: Effect of repeated ipsapirone treatment on hippocampal excitatory synaptic transmission in the freely behaving rat: role of 5-HT1A receptors and relationship to anxiolytic effect. Eur J Pharmacol 1997, 323:59-68.

[7] Cai JX, Ma YY, Xu L, Hu XT: Reserpine impairs spatial working memory performance in monkeys: reversal by the alpha 2-adrenergic agonist clonidine. Brain Res 1993, 614:191-196.

申请专利

[1]郝小江，杨小生，周俊，蔡景霞，徐林，胡新天。N-取代基-4-取代苯基-5-烷基-5-取代苄基吡咯烷酮-2，其中间体其合成方法及其应用。公开号：ZL94 1 04879.9

[2]蔡景霞，郝小江，王永富，徐林，杨小生，汪冶。芬克罗酮的应用。公开号：CN1759831A

[3]郑云峰，王江，徐林。中枢神经系统磁刺激电路、装置、用途及其使用方法。国际专利申请号：PCT/CN2006/001289

[4]陈纪军、徐林、周俊、吕俊、毛榕榕、田孟、张雪梅、沈勇、顾燕华、马云保、左爱学、程辟、江志勇。 5-甲基-1，3苯二酚及其衍生物在制备抗抑郁药物和功能食品中的应用。国内专利申请号：200710066098.1

[5]陈纪军，徐林，周俊，吕俊，毛榕榕, 田孟，张雪梅，沈勇，顾燕华, 马云保，左爱学，程辟，江志勇。 2，5-二羟基苯甲醇衍生物在制备抗抑郁药物和功能食品中的应用。国内专利申请号：200710066088.7

[6]陈纪军，徐林，周俊，吕俊，毛榕榕，田孟，周启心，张雪梅，沈勇，江志勇，左爱学。5-甲基-1,3苯二酚或其衍生物用于制备或预防抑郁症的药物或功能食品中的用途。国际专利申请号：PCT/CN2008/071752

[7]陈纪军，徐林，周俊，吕俊，毛榕榕，田孟，周启心，张雪梅，沈勇，江志勇，左爱学。2,5-二羟基苯甲醇或其衍生物在制备或预防抗抑郁症药物或功能食品中的用途。国际专利申请号：PCT/CN2008/071757

 

奖励

1999 中国科学院“百人计划”和国家基金委杰出青年

2002 云南省科技进步一等奖“恒河猴工作记忆的儿茶酚胺受体机制研究”

2007 国务院政府特殊津贴

2008 谈家桢生命科学创新奖

图1实验室全家福

 

图 2 师生交流

 

图 3 同行来访实验室

图 4 转基因小鼠

图5 清醒自由移动大鼠

 

 

图6 测试焦虑行为的小鼠高架十字迷宫

图7 麻醉大鼠电生理记录

图8大鼠恐惧记忆测试

图9大鼠水迷宫实验

图10 大鼠条件性位置偏爱实验

图11 测试焦虑行为的小鼠黑白箱实验

图12 测试抑郁样行为的小鼠悬尾实验

图12 小鼠转轮实验