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,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,#,学 习 与 记 忆,Learning&Memory,北京大学 神经科学研究所,Neuroscience Research Institute,Peking University,主讲教师,:,王韵,Neuroscience,概述,Introduction,Behavior,Genes,Environment,Learning and memory,Beneficial,Harmful,Interesting questions,What are major forms of learning?,What types of information about the environment,are learned most easily?,Do different types of learning give rise to different,memory processes?,How is memory stored and retrieved?,目录,Contents,概念,Concepts,学习,及记忆的基本过程,Process of Learning and Memory,学习的基本类型,Ways of Learning,记忆的基本类型,Ways of Memory,学习及记忆的突触机制,Synaptic Mechanisms of Memory,中枢突触可塑性与学习记忆,Central Synaptic Plasticity and Learning&Memory,学习及记忆的分子机制,Molecular Mechanisms of Memory,递质的调节,Regulation of Neurotransmitters,Neuroscience,概念,Concepts,学习,(,Learning,),：,the process by which we acquire knowledge about the world via the nerve system,人或动物通过神经系统接受外界环境信息而影响自身行为,记忆,(,Memory,),：,the process by which that knowledge is encoded,stored and later retrieved,获取的信息或经验在脑内贮存和提取,(,再现,),的神经活动过程,Return,Neuroscience,学习与记忆的基本过程,(Process of Learning and Memory),Acquired or encoded,获得,(,识记或登陆,),：感知外界事物或接受外界信息,(,外界刺激,),的阶段，也即通过感觉系统向脑内输入讯号,学习过程,Consolidated,巩固：获取的信息在脑内编码贮存和保持的阶段,Retrieved,再现：将贮存于脑内的信息提取出来使之再现于意识中的过程回忆过程,return,Neuroscience,非联合型学习,Nonassociative learning,学习的基本形式,Ways of Learning,习惯化,habituation,repeat non-noxious stimuli-reduced response,敏化,Sensitization-,harmful stimulivigorously response to all stimuli,联合型学习,Associative learning,经典式条件反射,Classical conditioned reflex,操作性条件反射,Operant conditioned reflex,或称器具性条件反射,Instrumental conditioned reflex,Return,Neuroscience,记忆的基本形式,Ways of Memory,First Order,Memory,Sensory Memory,外,界,信,息,输,入,遗忘,（信息丢失）,注意,不,重,复,遗忘,Second Order,Memory,重复,Third Order,Memory,可能,遗忘,再现,终生,不忘,Short-term Memory,Long-term Memory,不,注,意,Neuroscience,按时程进行分类,记忆时程及其特点的比较,记忆时程,信息贮存时间,(S),脑内可能的神经机制,举例,感觉性记忆,1,感觉讯号传向大脑，在皮层感觉区传递的时程,在查找字典上的某个词时，对其他的词一闪而过,第一级记忆,数秒钟,特定的神经信息在有关神经通路中往返传递一短时间，其化学机制可能是关键大分子的可逆性构象变化,查到一个电话号码，拨完后即忘,第二级记忆,数分钟至若干年,蛋白质合成增加，突触功能增强及突触结构修饰等。神经信息影响,mRNA,或基因表达,经历中的重要事件,第三级记忆,终生,脑内新突触形成或突触结构不可逆变化,本人姓名，年龄、生日等,Return,按信息储存和回忆的方式分类,陈述性记忆,(declarative memory),或称外显性记忆,(explicit memory),进入意识系统，比较具体，可以清楚地描述,非陈述性记忆,(nondeclarative memory),，反射性记忆（,reflexive memory,）或称内隐性记忆,(implicit memory),无意识成分参加，只涉及刺激顺序的相互关系，贮存各事件间相关联的信息，只有通过程序性的操作过程才能体现出来,Neuroscience,陈述式记忆与非陈述式记忆的区别,陈述式记忆,非陈述式记忆,含义,进入意识系统，比较具体，可以清楚描述,无意识成分参与，只涉及刺激与顺序之间的相互关系，贮存各个事件之间相互关联的信息，只有通过顺序性操作过程才能体现出来,速度,快,慢,参与的脑结构,大脑皮层及某些特异的脑区,(,内侧颞叶及间脑,),只激活与该项记忆有关的感觉系统和运动系统,纹状体技巧，习惯,简单的经典条件反射杏仁核，小脑,突触水平机制,突触前与突触后神经元同时兴奋的联合机制,突触前神经元的易化机制：突触前神经元与有关的调制神经元的联合机制,脑内记忆系统,陈述性记忆的神经回路需要边缘系统参与,大脑皮层,V1V2,V3,V4,边缘系统,内侧颞叶 内侧丘脑 腹内侧额叶,基底前脑胆碱能系统,Neuroscience,颞下回,嗅皮层、杏仁复合体和海马,Motimer Mishkin,非陈述性记忆的神经回路边缘系统及运动系统共同参与,大脑皮层,尾 核,苍 白球,运 动系统,丘脑,边 缘系统,伏隔核,VIP,GLu,GABA,GABA,DA,Neuroscience,学习记忆的神经基础,短时记忆与长时记忆是整个记忆过程的不同阶段,具有不同的神经机制,短时记忆的读出机制易受影响,长时记忆相对稳定,短时记忆,神经可塑性变化,长时记忆,与脑内某些长期性的功能和结构,新蛋白质的合成,Neuroscience,非联合型学习记忆的机制,记忆的突触机制,Synaptic Mechanisms of Memory,联合型学习记忆的机制,习惯化的机制,突触效能减弱,敏化的机制,突触前易化,时间特异的、活动依赖的突触前易化,Fig,Fig,Fig,Return,Neuroscience,突触效能减弱的机制,习惯化的机制,Mechanisms of hibituation,突触前感觉神经元末梢递质释放量减少,递质释放减少的可能机制,可动员的突触囊泡数目减少,Return,Neuroscience,突触前膜,N,型,Ca,2+,通道失活,敏化的机制,Mechanisms of,Short Term Sensitization,突触前易化的机制,突触前易化使突触效能增强,Gs-protein,ATP,cAMP,PKA,激 活,K,+,channel,关闭,AP,时程,Return,AC,Neuroscience,5-HT,感觉神经元,5-HTR,中间神经元,K,+,电导,Ca,2+,内流,N-type Ca,2+,Channel open,L-type Ca,2+,Channel open,vesicle mobilized to active zone,Transmitter release,Go-protein,PLC,DAG,PKC,联合型学习的突触机制,Return,Neuroscience,K,+,channel,关闭,K,+,电导,AP,时程延长,Ca,2+,内流,CS,AC,激活,5-HT 5-HTR,Ca,2+,内流,US,G-Protein,cAMP,特异的、时间依赖的突触前易化,突触前易化的可能的分子机制,Fig,Fig,Neuroscience,LTP in mossy fiber pathway is non-NMDA mediated,presynaptic induction,nonassociative,Ca,2+,influx in presynaptic neuron,cAMP,PKA activated,b,-adrenergic receptors,adenylyl cyclase,CA3,长时程增强（,Long-Term Potentiation,LTP,）,海马的长时程增强海马的结构,Modulatory input,LTP in CA1,LTP in CA1 is associative,，,NMDA receptor dependent,presynatic and postsynaptic induction,Two features differ from that of LTP in CA3,Cooperativity(,协同性,),:requires activation of several,afferent axons together,Associativity(,联合性,),：,requires concomitant activity,in both presynaptic and,postsynaptic cells to adequately,depolarize the postsynaptic cell,LTP,产生的必要条件,Activation of synapse,Strong depolarization of postsynaptic cell in CA1,引起突触后神经元去极化的条件,As high as enough frequency,EPSP temporal summation,As many as enough synapse,EPSP spatial summation,诱导,CA1 LTP,产生的突触后因素,postsynatic depolarizaion,activation of NMDA receptors,influx of Ca,2+,activation by Ca,2+,of,several second-messenger systems in the postsynaptic cell,Neuroscience,LTP Has a Transient Early and a Consolidated Late Phase,Early LTP,-one stimulus train produces an early,short term phase of LTP,lasting 1-3 hours-No new protein synthesis,Late LTP,-,Four or more trains induce a more persistent phase of LTP that lasts at least 24 hoursrequires new protein and RNA synthesis,Mechanisms of Early LTP
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