導(dǎo)論 -神經(jīng)回路

1、神經(jīng)環(huán)路張 智2013.10.31神經(jīng)系統(tǒng)主要包含神經(jīng)細(xì)胞和膠質(zhì)細(xì)胞，通過突觸聯(lián)系等方式形成復(fù)雜的神經(jīng)網(wǎng)絡(luò)，完成神經(jīng)系統(tǒng)的各種功能活動(dòng)。Intact/behaviorNetworkCellularSynapticMolecularNeuronal Circuits2不同性質(zhì)和功能得神經(jīng)元通過各種形式的復(fù)雜連接，在不同水平構(gòu)成 神經(jīng)環(huán)路（neural circuit)和神經(jīng)網(wǎng)絡(luò)(neural network)，以類似串聯(lián)、并聯(lián)、前饋、反饋、正反饋、負(fù)反饋等多種形式活動(dòng)。其中最簡單的神經(jīng)環(huán)路是三突觸機(jī)構(gòu)。即上一級(jí)神經(jīng)元的軸突分枝一方面興 奮一個(gè)主神經(jīng)元，另一方面通過興奮中間神經(jīng)元抑制該主神經(jīng)元，從

2、 而在一個(gè)最小的環(huán)路上達(dá)到興奮與抑制的平衡。更復(fù)雜的神經(jīng)環(huán)路可見于神經(jīng)網(wǎng)絡(luò)的不同層次水平。在環(huán)路中興奮性與抑制性活動(dòng)相互作用，其最終效應(yīng)取決于許多神經(jīng)元活動(dòng)正負(fù)相消后的凈值，也就是神經(jīng)活動(dòng)的整合作用。3Basic models of neural circuits4神經(jīng)系統(tǒng)中樞神經(jīng)系統(tǒng)（Central nervous system, CNS)外周神經(jīng)系統(tǒng)（Peripheral nervous system, PNS）5Distinct subsystems all have characteristic circuitsStretch reflexConnectivity between th

3、e cortex to the thalamus6內(nèi)分泌高級(jí)功能神經(jīng)系統(tǒng)大腦皮層脊髓姿勢(shì)運(yùn)動(dòng)基底神經(jīng)節(jié)腦干小腦7/38翻正反射（righting reflex） 正常動(dòng)物可保持站立姿勢(shì)，若將其推倒則可翻正過來。頭部：刺激視覺和內(nèi)耳迷路引起反正頭與軀干：刺激頸部關(guān)節(jié)韌帶及肌肉（翻身中樞在頸部脊髓， 受高級(jí)中樞調(diào)控）8/38中樞對(duì)軀體感覺的分析感覺傳入通路三級(jí)神經(jīng)元接替大腦皮層第三級(jí)神經(jīng)元：丘腦的感覺接替核第二級(jí)神經(jīng)元：脊髓后角、腦干第一級(jí)神經(jīng)元：脊髓神經(jīng)節(jié)、腦神經(jīng)節(jié)9/21p 脊髓 脊髓位于脊椎骨的椎管中。 灰質(zhì)：蝴蝶狀核心部位，由神經(jīng)元胞體組成。分為： 背角、側(cè)角、腹角 白質(zhì)：由沿脊髓上行和下

4、行的長的軸突組成。分為： 背柱、側(cè)柱、腹柱 脊神經(jīng)是PNS的一部分，通過椎骨間孔與脊髓相聯(lián)系。 背根包含感覺軸突，腹根包含運(yùn)動(dòng)軸突。生理學(xué)第十章第二節(jié)神經(jīng)系統(tǒng)的感覺分析功能10/21運(yùn)動(dòng)傳出的最后公路（一）脊髓和腦干運(yùn)動(dòng)神經(jīng)元 脊髓運(yùn)動(dòng)神經(jīng)元和腦運(yùn)動(dòng)神經(jīng)元接受來自外周和中樞的傳入信息，產(chǎn)生反射，調(diào)節(jié)運(yùn)動(dòng)和姿勢(shì)，是運(yùn)動(dòng)反射的最后公路（final common path）。 運(yùn)動(dòng)神經(jīng)元胞體較大，主要支配梭外肌纖維； 神經(jīng)元胞體較神經(jīng)元小，主要支配梭內(nèi)肌纖維。 1906年，Sir Charles Sherrington出版了神經(jīng)系統(tǒng)的整合作用（The Integrative Action of th

5、e Nervous System）一書，收錄了1904年在耶魯大學(xué)的講座內(nèi)容，共十章。這是一部對(duì)現(xiàn)代神經(jīng)生物學(xué)影響深遠(yuǎn)的著作。在書中，謝靈頓解決了當(dāng)時(shí)關(guān)于神經(jīng)系統(tǒng)“Reticular Theory”和“Neuron Doctrine”的爭論（傾向于后者）；并提出了諸多我們今天所熟悉的基本概念和術(shù)語。 在第四章研究反射的相互作用時(shí)，謝靈頓引入了“common path”的概念，將“private”和“public path”區(qū)分開。所謂“public”， 是指會(huì)聚式接受諸多傳入的神經(jīng)元。在運(yùn)動(dòng)反射通路中，中間神經(jīng)元接受會(huì)聚式輸入，是“common path”；但它們都通過最終支配骨骼肌的運(yùn)動(dòng)神經(jīng)

6、元（motorneuron）起作用。因此，運(yùn)動(dòng)神經(jīng)元是最后（final）公路（common path）。11/38Brain (2007) 130 (4): 887-894.（二）運(yùn)動(dòng)單位（motor unit） 概念：由一個(gè)運(yùn)動(dòng)神經(jīng)元或腦運(yùn)動(dòng)神經(jīng)元及其支配的全部肌纖維組成的功能單位。 神經(jīng)支配率（運(yùn)動(dòng)神經(jīng)元與支配肌纖維的比） 一個(gè)眼外肌運(yùn)動(dòng)神經(jīng)元支配612根肌纖維： 精細(xì)運(yùn)動(dòng) 一個(gè)三角肌運(yùn)動(dòng)神經(jīng)元支配2000根肌纖維：產(chǎn)生巨大的肌張力12/381、脊髓休克（spinal shock） 定義：脊髓與高位中樞之間離斷后，反射活動(dòng)暫時(shí)喪失而進(jìn)入無反應(yīng)狀態(tài)。 表現(xiàn)：橫斷面以下脊髓所支配的軀體和內(nèi)臟反

7、射減退以至消失，如骨骼肌緊張降低，甚至消失，外周血管擴(kuò)張，血壓下降，發(fā)汗反射消失，大小便潴留。 離斷面水平以下的知覺和隨意運(yùn)動(dòng)能力將永久喪失。13/382、脊髓對(duì)姿勢(shì)的調(diào)節(jié) 姿勢(shì)反射：CNS可通過調(diào)節(jié)骨骼肌的緊張度或產(chǎn)生相應(yīng)的運(yùn)動(dòng)，以保持或改正軀體在空間的姿勢(shì)。14/38Migraine headachesCervical spondylopathyScapulohumeral periarthritisViscera painJoint painBack pain牽涉痛（referred pain） 內(nèi)臟疾病引起遠(yuǎn)隔的體表部位感覺疼痛或者痛覺過敏。 心肌缺血心前區(qū)、左肩、左上臂 膈中央部受刺

8、激 肩上部 胃潰瘍和胰腺炎 左上腹和肩胛間 膽囊炎 右肩部 闌尾炎上腹部或臍周 腎結(jié)石腹股溝區(qū)Why?17/21自主神經(jīng)系統(tǒng)（autonomic nervous system，ANS） 又稱內(nèi)臟神經(jīng)系統(tǒng) 功能：調(diào)節(jié)內(nèi)臟，心血管和腺體的活動(dòng) 包括傳入（感覺）神經(jīng)和傳出（運(yùn)動(dòng)）神經(jīng)；習(xí)慣上僅指其傳出部分 分為交感神經(jīng)系統(tǒng)和副交感神經(jīng)系統(tǒng) 自主反射，中樞控制18/12（一）自主神經(jīng)的結(jié)構(gòu)特征 由節(jié)前和節(jié)后兩個(gè)神經(jīng)元組成。 節(jié)前B類纖維，傳導(dǎo)速度快；節(jié)后C類纖維，傳導(dǎo)速度慢。 交感神經(jīng)節(jié)位于椎旁節(jié)和椎前節(jié)，節(jié)前纖維短，節(jié)后纖維長； 副交感神經(jīng)節(jié)位于效應(yīng)器官，節(jié)前纖維長，節(jié)后纖維短。 交感起自脊髓胸、腰

9、段，副交感起自腦干的腦神經(jīng)核和脊髓骶段。 交感幾乎支配所有內(nèi)臟器官，節(jié)前與節(jié)后輻散程度高，興奮時(shí)效應(yīng)廣泛； 副交感分布局限，節(jié)前與節(jié)后輻散程度低，興奮時(shí)效應(yīng)局限。 皮膚和肌肉血管、一般的汗腺、豎毛肌、腎上腺髓質(zhì)和腎只有交感神經(jīng)支配。19/12（二）自主神經(jīng)系統(tǒng)的功能 調(diào)節(jié)心肌、平滑肌和腺體的活動(dòng) 遞質(zhì)： Ach：交感節(jié)前，副交感節(jié)前、節(jié)后 NE：交感節(jié)后20/12（三）自主神經(jīng)系統(tǒng)的功能特征.緊張性支配對(duì)同一效應(yīng)器的雙重支配受效應(yīng)器所處功能狀態(tài)的影響對(duì)整體生理功能調(diào)節(jié)的意義交感：動(dòng)員機(jī)體的潛在能力，適應(yīng)環(huán)境的急劇變化。副交感：保護(hù)機(jī)體，休整恢復(fù)，促進(jìn)消化，積蓄能量，加強(qiáng)排泄和生殖

10、功能。21/12大腦神經(jīng)環(huán)路基底神經(jīng)節(jié)與大腦皮層之間的纖維聯(lián)系大腦皮層興奮性谷氨酸興奮性谷氨酸丘腦前腹核（VA） 丘腦外側(cè)腹核（VL）基底神經(jīng)節(jié)較復(fù)雜直接通路間接通路22/38大腦皮層的感覺代表區(qū)1、體表感覺代表區(qū)（1）第一感覺區(qū)： 中央后回（S1） Brodmann分區(qū)的3-1-2區(qū)（2）第二感覺區(qū)： 大腦外側(cè)溝的上壁，中央后回底部延伸到腦島的區(qū)域（S2）2、本體感覺代表區(qū) 中央前回（4區(qū)）生理學(xué)第十章第二節(jié)神經(jīng)系統(tǒng)的感覺分析功能23/21p 體表第一感覺區(qū)的特點(diǎn)：軀干四肢交叉投射，頭面部雙側(cè)投射； 投射區(qū)域大小與分辨精細(xì)程度有關(guān)； 總體倒置，頭面部正立；感覺皮層的感覺柱；感覺皮層的可塑性。

11、24/21皮層小腦功能參與隨意運(yùn)動(dòng)的設(shè)計(jì)和程序的編制。25基底神經(jīng)節(jié)與大腦皮層之間的纖維聯(lián)系大腦皮層+丘腦VA/VLGlu (+)基底神經(jīng)節(jié)傳出：蒼白球內(nèi)側(cè)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.穹窿扣帶回丘腦前核隔核額眶部皮質(zhì)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.下丘腦垂體腎上腺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.腹外側(cè)視前區(qū)結(jié)節(jié)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，又郁悶了！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