导论 -神经回路

1、神经环路张 智2013.10.31神经系统主要包含神经细胞和胶质细胞，通过突触联系等方式形成复杂的神经网络，完成神经系统的各种功能活动。Intact/behaviorNetworkCellularSynapticMolecularNeuronal Circuits2不同性质和功能得神经元通过各种形式的复杂连接，在不同水平构成 神经环路（neural circuit)和神经网络(neural network)，以类似串联、并联、前馈、反馈、正反馈、负反馈等多种形式活动。其中最简单的神经环路是三突触机构。即上一级神经元的轴突分枝一方面兴 奋一个主神经元，另一方面通过兴奋中间神经元抑制该主神经元，从

2、 而在一个最小的环路上达到兴奋与抑制的平衡。更复杂的神经环路可见于神经网络的不同层次水平。在环路中兴奋性与抑制性活动相互作用，其最终效应取决于许多神经元活动正负相消后的净值，也就是神经活动的整合作用。3Basic models of neural circuits4神经系统中枢神经系统（Central nervous system, CNS)外周神经系统（Peripheral nervous system, PNS）5Distinct subsystems all have characteristic circuitsStretch reflexConnectivity between th

3、e cortex to the thalamus6内分泌高级功能神经系统大脑皮层脊髓姿势运动基底神经节脑干小脑7/38翻正反射（righting reflex） 正常动物可保持站立姿势，若将其推倒则可翻正过来。头部：刺激视觉和内耳迷路引起反正头与躯干：刺激颈部关节韧带及肌肉（翻身中枢在颈部脊髓， 受高级中枢调控）8/38中枢对躯体感觉的分析感觉传入通路三级神经元接替大脑皮层第三级神经元：丘脑的感觉接替核第二级神经元：脊髓后角、脑干第一级神经元：脊髓神经节、脑神经节9/21p 脊髓 脊髓位于脊椎骨的椎管中。 灰质：蝴蝶状核心部位，由神经元胞体组成。分为： 背角、侧角、腹角 白质：由沿脊髓上行和下

4、行的长的轴突组成。分为： 背柱、侧柱、腹柱 脊神经是PNS的一部分，通过椎骨间孔与脊髓相联系。 背根包含感觉轴突，腹根包含运动轴突。生理学第十章第二节神经系统的感觉分析功能10/21运动传出的最后公路（一）脊髓和脑干运动神经元 脊髓运动神经元和脑运动神经元接受来自外周和中枢的传入信息，产生反射，调节运动和姿势，是运动反射的最后公路（final common path）。 运动神经元胞体较大，主要支配梭外肌纤维； 神经元胞体较神经元小，主要支配梭内肌纤维。 1906年，Sir Charles Sherrington出版了神经系统的整合作用（The Integrative Action of th

5、e Nervous System）一书，收录了1904年在耶鲁大学的讲座内容，共十章。这是一部对现代神经生物学影响深远的著作。在书中，谢灵顿解决了当时关于神经系统“Reticular Theory”和“Neuron Doctrine”的争论（倾向于后者）；并提出了诸多我们今天所熟悉的基本概念和术语。 在第四章研究反射的相互作用时，谢灵顿引入了“common path”的概念，将“private”和“public path”区分开。所谓“public”， 是指会聚式接受诸多传入的神经元。在运动反射通路中，中间神经元接受会聚式输入，是“common path”；但它们都通过最终支配骨骼肌的运动神经

6、元（motorneuron）起作用。因此，运动神经元是最后（final）公路（common path）。11/38Brain (2007) 130 (4): 887-894.（二）运动单位（motor unit） 概念：由一个运动神经元或脑运动神经元及其支配的全部肌纤维组成的功能单位。 神经支配率（运动神经元与支配肌纤维的比） 一个眼外肌运动神经元支配612根肌纤维： 精细运动 一个三角肌运动神经元支配2000根肌纤维：产生巨大的肌张力12/381、脊髓休克（spinal shock） 定义：脊髓与高位中枢之间离断后，反射活动暂时丧失而进入无反应状态。 表现：横断面以下脊髓所支配的躯体和内脏反

7、射减退以至消失，如骨骼肌紧张降低，甚至消失，外周血管扩张，血压下降，发汗反射消失，大小便潴留。 离断面水平以下的知觉和随意运动能力将永久丧失。13/382、脊髓对姿势的调节 姿势反射：CNS可通过调节骨骼肌的紧张度或产生相应的运动，以保持或改正躯体在空间的姿势。14/38Migraine headachesCervical spondylopathyScapulohumeral periarthritisViscera painJoint painBack pain牵涉痛（referred pain） 内脏疾病引起远隔的体表部位感觉疼痛或者痛觉过敏。 心肌缺血心前区、左肩、左上臂 膈中央部受刺

8、激 肩上部 胃溃疡和胰腺炎 左上腹和肩胛间 胆囊炎 右肩部 阑尾炎上腹部或脐周 肾结石腹股沟区Why?17/21自主神经系统（autonomic nervous system，ANS） 又称内脏神经系统 功能：调节内脏，心血管和腺体的活动 包括传入（感觉）神经和传出（运动）神经；习惯上仅指其传出部分 分为交感神经系统和副交感神经系统 自主反射，中枢控制18/12（一）自主神经的结构特征 由节前和节后两个神经元组成。 节前B类纤维，传导速度快；节后C类纤维，传导速度慢。 交感神经节位于椎旁节和椎前节，节前纤维短，节后纤维长； 副交感神经节位于效应器官，节前纤维长，节后纤维短。 交感起自脊髓胸、腰

9、段，副交感起自脑干的脑神经核和脊髓骶段。 交感几乎支配所有内脏器官，节前与节后辐散程度高，兴奋时效应广泛； 副交感分布局限，节前与节后辐散程度低，兴奋时效应局限。 皮肤和肌肉血管、一般的汗腺、竖毛肌、肾上腺髓质和肾只有交感神经支配。19/12（二）自主神经系统的功能 调节心肌、平滑肌和腺体的活动 递质： Ach：交感节前，副交感节前、节后 NE：交感节后20/12（三）自主神经系统的功能特征.紧张性支配对同一效应器的双重支配受效应器所处功能状态的影响对整体生理功能调节的意义交感：动员机体的潜在能力，适应环境的急剧变化。副交感：保护机体，休整恢复，促进消化，积蓄能量，加强排泄和生殖

10、功能。21/12大脑神经环路基底神经节与大脑皮层之间的纤维联系大脑皮层兴奋性谷氨酸兴奋性谷氨酸丘脑前腹核（VA） 丘脑外侧腹核（VL）基底神经节较复杂直接通路间接通路22/38大脑皮层的感觉代表区1、体表感觉代表区（1）第一感觉区： 中央后回（S1） Brodmann分区的3-1-2区（2）第二感觉区： 大脑外侧沟的上壁，中央后回底部延伸到脑岛的区域（S2）2、本体感觉代表区 中央前回（4区）生理学第十章第二节神经系统的感觉分析功能23/21p 体表第一感觉区的特点：躯干四肢交叉投射，头面部双侧投射； 投射区域大小与分辨精细程度有关； 总体倒置，头面部正立；感觉皮层的感觉柱；感觉皮层的可塑性。

11、24/21皮层小脑功能参与随意运动的设计和程序的编制。25基底神经节与大脑皮层之间的纤维联系大脑皮层+丘脑VA/VLGlu (+)基底神经节传出：苍白球内侧部26Neuronal circuits in the brainCircuits of HippocampusHPAaxisCircuits of AmygdalaHippocampusIt belongs to the limbic system and plays important roles in the consolidation of informationfrom short-term memory to long-term

12、 memory and spatial navigation.Hippocampus1.Anatomy of hippocampusThe hippocampus was mainly divided into four areas: CA1、CA2、CA3 and CA4.1.1 Cell typesPyramidal cells: modulate the network in the local regions. GluAchInterneurons: provide long projectons with different regions. GABAGranule cells.Gl

13、uDy2. Microcircuits of hippocampus2.1 InputsMajor inputs come from the entorhinal cortex, which in turn communicate inputs from the cingulate, temporal, orbital, and olfactory cortices and amygdala to the hippocampus.穹窿扣带回丘脑前核隔核额眶部皮质嗅球2.2OutputsOutputs or efferents from the hippocampus pass directly

14、 from the subiculum to theentorhinal cortex and amygdala or through the fornix to a variety of anterior structures.2.3 Papez circuitsThe Papez circuit plays a role in the cortical control of emotion and storing memory.Networks of 2.4 Microcircuits in hippocampus1.Perforant

15、 path-Dentata Gyrus pathway (PP-DG pathway)entorhinal cortexperforant pathdentate gyrus2.Mossy Fibre-CA3 pathway (MF-CA3 pathway)mossy fibersdentate gyrus granule cellsCA33.CA3-CA1 pathwaypyramidal neuronsSchaffer collateralsCA1Neuroscience exporing the brain third edition2.5 Information flow throug

16、h the hippocamusA major flow of information through the hippocampus is a one-way circuit.3. Functions 3.1 Role in memorySevere damage to the hippocampus in both hemispheres results in profound difficulties in formingnew memories and often also affects memories formed before the damage occurred.Who a

17、m I ?3.2 Role in spatial learning and navigationThere are some “place cells”in the hippocampus, they can decide where they are andwhere they go.Do not be out !The cat is there !Spatial firing patterns of 8 place cells recorded from the CA1 layer of a rat. The rat ran back and forth along an elevated

18、 track, stopping at each end to eat a small food reward. Dots indicate positions where action potentials were recorded, with colorindicating which neuron emitted that action potential.3.3 Role in healthThere are also many diseases relate to hippocampus, such as AD, Epilepsy, Transient globalamnesia

19、, Schizophrenia and anxiety.EpilepsySchizophreniaHPAaxisThe HPA is abbreviation of HypothalamicPituitaryAdrenal axis.下丘脑垂体肾上腺1. HypothalamusIt has important functions, such as food intake and energy expenditure. Dysfunctions in hypothalamic circuitry result in，emotional disorders, obesity/anorexia a

20、nd impairment of cognitive function. Information flow withinneural circuitry relies on synaptic transmission of There are reciprocally interaction between amygdala,hippocampus and hypothalamus. Thehippocampus can mediate the HPA axis activity at the hypothalamus level. F

21、unctionsThe HPA axis has relationship with mood disorders and physical diseases, such as anxietydisorder, bipolar disorder, major depressive disorder, fibromyalgia, alcoholism.caused insomnia.The hypothalamus also mediates sleep and circadian rhythms with bainstem.Hypothalamus involved in the ascend

22、ing arousal system and lesion of hypothalamus.腹外侧视前区结节核NATURE|Vol 437|27 October 2005 |doi:10.1038/ nature04284SomeantidepressantsmainlyactontheHPAaxis,suchasCitalopram,Escitalopram, Paroxetine, Fluoxetine, Fluvoxamine, Sertraline and so on.They areall serotonin (5-TH) reuptake inhibitors.As the dys

23、function of the HPA axis may result in depression, there are many potentialtargets in the HPA axis, such as CRF receptors agonists and glucoeorticoid receptors agonists.哎，又郁闷了！There are also many functions of the body involve the HPA axis, such as digestion,immune system, sex and the storage and con

24、sumption of energy.你才是胖子！The network of the HPA axisAmygdalaAmygdala is the integrative center for emotional behavior, and motivation.1. Anatomicalsubdivisions2. Circuits of amygdala2.1 Inputs of the AmygdalaInputs or afferents to the amygdala via the stria terminalis, ventral amygdalofugal pathway,

25、olfactory stria, and directly from temporal lobe 2.2 Majore output pathways of the Amygdala1.Ventral amygdalofugal pathway 2.Strial terminalis3. Directly to the hippocampus4. Directly to the entorhinal cortex5. Directly to the dorsomedial nucleus of the thalamu

26、3. Neuropsychological correlates of amygdala activity3.1 FearThe patients with amygdala lesion fail to exhibit fear-related behaviors and recognize the fear expresssions. This finding reinforces the conclusion that the amygdala “plays apivotal role in triggering a state

27、of fear”.The word ismine !3.2 SocialInteractionAmygdala volume correlates positively with both the size and the complexity of socialnetworks. Individuals with larger amygdala had larger and more complex social networks.Amygdala lesions knock out the evaluative process, re

28、sulting in default trust and lack of negative evaluations.3.3 AggressionAnimal studies have shown that stimulating the amygdala appears to increase aggressivebehavior. Likewise, studies using brain lesions have shown that harm to the amygdala mayproduce the opposite effect.3.4 Hemispheric specializa

29、tionsThere are functional differences between the right and left amygdala. In one study, electrical stimulations of the right amygdala induced negative emotions, especially fear and sadness. In contrast, stimulation of the left amygdala was able to induce either pleasant or unpleasantemotions.3.5 Alcoholism and binge dri