中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性培訓(xùn)課件

1、中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性誘導(dǎo)(induction) ：指胚胎發(fā)育過程中兩種細(xì)胞群落通過分子間的相互作用使其中一個群落或兩個群落發(fā)生定向分化的過程。提供或傳遞誘導(dǎo)分子的細(xì)胞是誘導(dǎo)者( inductor)，接受這種分子的細(xì)胞或結(jié)構(gòu)稱反應(yīng)者( reactor)。結(jié)構(gòu)發(fā)育：神經(jīng)上皮腦和脊髓構(gòu)筑神經(jīng)環(huán)路發(fā)育或構(gòu)筑：神經(jīng)元發(fā)生突觸形成可塑性(plasticity)：即神經(jīng)系統(tǒng)發(fā)育過程中神經(jīng)元對神經(jīng)活動及環(huán)境改變所作出的結(jié)構(gòu)和功能上的應(yīng)答反應(yīng)。細(xì)胞調(diào)亡 - 突觸重排及消退等Introduction2中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性O(shè)utline Ectoderm - neural tube - brain an

2、d spinal cord (review) The genesis of neurons The genesis of connections (synapse formation) The elimination of cells and synapses Activity-dependent synaptic rearrangement The Elementary Mechanisms of Cortical Synaptic Plasticity Importance of the critical period Concluding Remarks3中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性Fro

3、m neural tube to the initial brain and spinal cord The entire nervous system arises from the ectoderm The induction and patterning of the nervous system 4中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性神經(jīng)板期神經(jīng)褶期 (C) 神經(jīng)管期脊椎動物神經(jīng)管的形成:神經(jīng)管有兩個主要的軸線：背腹軸和前后（頭尾）軸。前后軸將神經(jīng)系統(tǒng)分成前腦、中腦、后腦和脊髓，還將這些區(qū)域細(xì)分為更加特殊的神經(jīng)結(jié)構(gòu)。在背腹軸上，不同的區(qū)域也有不同的神經(jīng)細(xì)胞種類。在有些部位，還有左右軸，即左右兩側(cè)

4、分布不同的神經(jīng)細(xì)胞。外周神經(jīng)系統(tǒng)來源于與神經(jīng)板相鄰的神經(jīng)脊，后者是外胚層中一群特殊的細(xì)胞，從發(fā)源地遷移到胚胎多個部位，形成包括外周神經(jīng)系統(tǒng)在內(nèi)的多種組織。即脊髓平面的神經(jīng)系統(tǒng)及其周圍組織，背側(cè)在上，腹側(cè)在下。5中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性The neural plate is induced by signals from adjacent mesodermThe neural plate is patterned along its dorso-ventral axis by signals from adjacent non-neural cells The ventral NT the n

5、otochord The dorsal NT the epidermal ectoderm The neural tube (NT) formationneural plateneural grooveneural foldneural tubeneural tube6中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性Cranial neuropore anlage brainanlage spinal cordCaudal neuroporeCNS The neural tube formation7中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性A sample in human embryo-developing in fourth

6、 to fifth week. Showing neural fold，cranial neuropore，somite， caudal neuropore, etc. 8中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性 三個原始腦泡是腦的原基 前腦泡中腦泡菱腦泡 （后）前N孔閉合腦 泡Brain vesicle端腦 間腦后腦末腦第三腦室左、右大腦半球兩個側(cè)腦室背：四疊體腹：大腦腳 中腦腦橋、小腦延髓腦泡腔第四腦室中：中腦導(dǎo)水管9中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性10中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性基本保持三層結(jié)構(gòu)邊緣層白質(zhì)套層脊髓灰質(zhì)管腔中央管兩側(cè)壁套層神經(jīng)母細(xì)胞和成膠質(zhì)細(xì)胞的迅速增生而增厚神經(jīng)管頂壁和底壁薄而窄 神經(jīng)管的尾側(cè)

7、段分化、發(fā)育為脊髓腹側(cè)兩基板背側(cè)兩翼板頂 板底 板11中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性 胚胎第三個月之前，脊髓與脊 柱等長，其下端達(dá)脊柱的尾骨； 胚三個月后，因脊柱增長快于 脊髓，脊柱便漸超越脊髓向尾 端延伸，脊髓位置相對上移； 出生前，脊髓下端與第三腰椎 平齊，僅以終絲與尾骨相連； 節(jié)段分布的脊神經(jīng)均在胚胎早 期形成，從相應(yīng)節(jié)段的椎間孔 穿出，脊髓位置上移后，脊髓 頸段以下的脊神經(jīng)根便斜向尾 側(cè)，至腰、骶、尾段的脊神經(jīng) 根則在椎管內(nèi)垂直下行，與終 絲共同組成馬尾。12中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性Normal Anencephaly spinal bifida13中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性發(fā)育異常是指

8、由于各種因素導(dǎo)致的先天畸形。狹義的概念僅指出生時(shí)解剖結(jié)構(gòu)畸形。廣義的包括出生時(shí)各種解剖結(jié)構(gòu)畸形、功能缺陷及代謝、遺傳行為的發(fā)育異常。據(jù)WHO(1966) 調(diào)查了包括16個國家的25個醫(yī)學(xué)中心的421781次妊娠，發(fā)現(xiàn)嚴(yán)重畸形占0.46%，輕度畸形占1.27%，總發(fā)生率為1.73%。我國1986-1987年作為國家攻關(guān)課題進(jìn)行了大規(guī)模的出生缺陷調(diào)查，對全國29個省市自治區(qū)的945所醫(yī)院124萬多圍產(chǎn)兒進(jìn)行了監(jiān)測，發(fā)現(xiàn)出生缺陷的總發(fā)生率平均為1.301%一些流行病學(xué)調(diào)查結(jié)果顯示某些出生類型的缺陷，發(fā)生率與地理?xiàng)l件有密切關(guān)系。山西省出生缺陷總發(fā)生率最高，湖北省最低 中樞神經(jīng)系統(tǒng)發(fā)育異常并不少見14中

9、樞神經(jīng)系統(tǒng)發(fā)育和其可塑性中樞神經(jīng)系統(tǒng)畸形絕大部分是由于神經(jīng)管發(fā)育缺陷或神經(jīng)管前后孔未閉引起,占總先天畸形發(fā)病率的17.主要是無腦畸形、隱性脊柱裂、脊髓脊膜膨出，腦積水等。此外，腦過小畸形、胼胝體不發(fā)育、苯丙酮尿癥、精神發(fā)育遲滯等均屬神經(jīng)系統(tǒng)的發(fā)育異常，但較少見。遺傳因素：包括單基因遺傳性疾患，多基因遺傳性疾患及染色體??；環(huán)境因素：包括藥物和環(huán)境化學(xué)物質(zhì)、微生物感染、電離輻射、母體疾病等因素。此外，營養(yǎng)因素如已知某些維生素缺乏，特別是葉酸缺乏可影響神經(jīng)管的正常封閉。 導(dǎo)致發(fā)育畸形的因素遠(yuǎn)未完全清楚15中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性The first step in wiring the nervou

10、s system together is the generation of neurons. Neuronal structure develops in three major stages: 1. Cell proliferation2. Cell migration 3. Cell differentiation The genesis of neurons16中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性Inducting factorsmesodermNeuronal progenitorGlial progenitorNeural progenitorectodermcell proliferati

11、on - Induction during neuronal genesis17中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性背唇可以誘導(dǎo)兩棲類動物胚胎形成第二條神經(jīng)軸：（A）斯佩曼和曼葛得的組織塊移植實(shí)驗(yàn)。將供體原腸胚早期的背唇移植到宿主胚胎的腹側(cè)以后，宿主會在應(yīng)該形成腹部表皮的位置，產(chǎn)生包括神經(jīng)板在內(nèi)的第二個體軸。(B) 神經(jīng)誘導(dǎo)的分子模型。背唇中胚層細(xì)胞分泌的Noggin、Chordin和Follistatin能阻止外胚層中的BMP家族蛋白與其受體結(jié)合，從而抑制BMP誘導(dǎo)表皮的產(chǎn)生，使背側(cè)外胚層形成神經(jīng)板。原腸胚期早期的兩棲類動物胚胎18中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性中胚層細(xì)胞能決定神經(jīng)系統(tǒng)的前后軸 （A）原腸

12、胚期晚期的兩棲類動物胚胎的組織結(jié)構(gòu)（前后軸中線水平的切面）；（B）用于解釋神經(jīng)板如何沿著前后軸分化的“雙信號”假說。 19中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性Where are neuron and glial cell from?glioblastNeural tube-MSCNeural-epitheliaNeuroblast 20中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性cell proliferation - To grow or multiply by rapidly producing new cellsneural tubeVentricular zoneMarginal zoneNeuroblastne

13、ural tube21中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性cell proliferation - a characteristic of the choreography of cell proliferation合成DNA時(shí)(S期)，其核位于靠近外側(cè)膜處，然后核又回到靠官腔的位置進(jìn)行有絲分裂(M期)，有絲分裂產(chǎn)生的子細(xì)胞又移行至外界膜，再合成DNA并重復(fù)其增殖周期。分裂后子細(xì)胞(daughter cell) 命運(yùn)(fate)如何決定于很多因素，其中非常重要的因素是基因表達(dá)(gene expression)的差異性,而基因表達(dá)的調(diào)控取決于transcription factors的類型。22中樞神經(jīng)系

14、統(tǒng)發(fā)育和其可塑性Both daughter cells cleaved vertically from the precursor remain in the ventricular zone to divide again and again.This mode of cell division predominates early in development expand the population of neuronal precursorThe both cells cleaved horizontally from the precursor, one migrates away

15、 to take up its position in the cortex, where it will never divide again. The other daughter remains in the ventricular zone to undergo more division.This mode predominates later in development neuronal precursor cell proliferation - The fate of the newly formed daughter cellsVentricular zone precur

16、sor cells repeated this pattern until all of the neurons of the cortex have been generated. The cleavage have been basically finished on pregnant fifth month in human.23中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性In human, most neocortical neurons are born between the fifth week and fifth month of gestation (pregnancy), peaking a

17、t the astonishing rate of 250,000 new neurons per minute.Research suggest: the gene expression of the precursor is regulated by its transcription factors( the proteins/upstream molecules ). See left figure.Notch-1 “unopposed” by numb, activates the gene expression that the cell to cease division and

18、 migrate away from the ventricular zone. cell proliferation - How does the cleavage plane during cell division determine the cells fate? - The distribution of cell constituents in precursor cells:24中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性Notch介導(dǎo)的信號傳導(dǎo)通路細(xì)胞之間可以通過對話來選擇不同的命運(yùn)（A）在果蠅的正常發(fā)育過程中，一個形成中的神經(jīng)前體細(xì)胞（深綠色）能阻止鄰近的神經(jīng)外胚層細(xì)胞（淺綠色）也選擇這一命運(yùn)

19、，使后者變成表皮細(xì)胞（白色）（B）形成中的神經(jīng)前體細(xì)胞通過Delta來激活鄰近的細(xì)胞中的Notch信號傳導(dǎo)通路，從而抑制AS-C和Delta等基因的表達(dá)，使鄰近的細(xì)胞不能成為神經(jīng)前體細(xì)胞（C）Notch活性的改變能影響果蠅神經(jīng)前體細(xì)胞的數(shù)量25中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性不對稱細(xì)胞分裂可以造成細(xì)胞的多樣性 （A）Numb蛋白的不對稱分布可以使兩個子細(xì)胞選擇不同命運(yùn)。集中在細(xì)胞一側(cè)的Numb蛋白（綠色）是否只分配給一個子細(xì)胞，還取決于紡錘體（粉紅色）的位置，即細(xì)胞分裂的平面（橙色）（B）果蠅的SOP細(xì)胞通過三輪不對稱的分裂產(chǎn)生組成感受機(jī)械或化學(xué)信息的外感覺（ ES）器官的四個細(xì)胞。Numb缺失或?qū)?/p>

20、稱分布都會影響ES器官的形成（C）Notch活性的改變也會影響ES器官的形成。H: 剛毛細(xì)胞；N：感覺神經(jīng)元；S: 毛孔細(xì)胞；Sh，鞘細(xì)胞。26中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性轉(zhuǎn)錄因子的按順序表達(dá)使神經(jīng)母細(xì)胞每次分裂后產(chǎn)生不同的神經(jīng)元 （A）在最早幾次分裂時(shí)，果蠅所有的神經(jīng)母細(xì)胞都會按順序表達(dá)四個轉(zhuǎn)錄因子（B）Hb和Kr缺失或持續(xù)表達(dá)能影響神經(jīng)母細(xì)胞產(chǎn)生不同GMC的能力。虛線顯示GMC或者死亡，或者變成二生（Hb缺失）或頭生（Kr缺失）GMC（C）、和這三個神經(jīng)母細(xì)胞每次分裂后產(chǎn)生的GMC各不相同，但用同樣的轉(zhuǎn)錄因子來決定它們的命運(yùn)。和前兩次分裂時(shí)都表達(dá)Hb。只分裂三次。運(yùn)動：運(yùn)動神經(jīng)元；中間：中間

21、神經(jīng)元；膠質(zhì)：膠質(zhì)細(xì)胞（D）神經(jīng)母細(xì)胞和GMC分裂時(shí)也將Numb蛋白不對稱地分配給兩個子細(xì)胞。GMC只分裂一次，產(chǎn)生兩個不同的神經(jīng)細(xì)胞，并通過Numb的不對稱分布使它們選擇不同的命運(yùn)27中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性Neurogenesis in the adult neocortexRecent finding show:Although most of the division action is over well before birth, the adult SGZ and SVZ retains some capacity to generate new neuron. Behavio

22、r/functional activity and environment Neurogenesis in the adult brain is far too limited to repair CNS damage.28中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性2. Cell migrationThe daughter cells from the precursors that immature neuron are called Neuroblast. A scaffold for the migration provided by the radial glial cells. the first

23、migration neuroblasts away from the ventricular form the cortical plate.This shows neuroblasts crawling along the thin processes of the radial glia route to the cortical plate, which forms just under the marginal zone29中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性A migrating cell recorded in tissue culture30中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性A:神經(jīng)細(xì)胞遷移過程

24、中,有領(lǐng)先突起。領(lǐng)先突起有分枝,動態(tài)競爭,其中一枝成為主干,帶領(lǐng)細(xì)胞體的移動,其后,又不斷重復(fù)分枝競爭,決定細(xì)胞移動方向。B:遷移的神經(jīng)細(xì)胞也可以原來領(lǐng)先突起的生長錐消失,在細(xì)胞體完全相反的一邊長處出新的突起,導(dǎo)致細(xì)胞180度轉(zhuǎn)向。遷移的神經(jīng)細(xì)胞:AB鼠腦SVZ細(xì)胞：肌動蛋白絲染綠色微管紅色31中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性 - Inside-out development of the cortex - the first cells to migrate to cortical plate from VZ that form subplate - As these differentiate

25、into neurons become layer VI in the cortical plate. - this process repeats again and again until all layers of the cortex the sublate neurons disappear 較早分化的較大神經(jīng)元先遷移并形成最內(nèi)層，依次順序向外；而較晚分化的較小神經(jīng)元則通過已形成的層次遷移并形成其外側(cè)新的層次；故不論皮質(zhì)的什么區(qū)域，其最內(nèi)層總是最早分化，而最外層則最后分化。32中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性哺乳動物大腦新皮層功能區(qū)域的形成 （A）在正常發(fā)育過程中，胚胎前腦背部中線和頭端的

26、成型中心分泌BMP、Wnt和FGF8等因子，使這些蛋白分別沿背腹軸和前后軸形成濃度梯度，進(jìn)而影響多種轉(zhuǎn)錄因子在神經(jīng)前期細(xì)胞中的表達(dá)量，最終把大腦新皮層分化成不同的功能區(qū)域。（B）受在胚胎前腦后端異位表達(dá)的FGF8影響，大腦新皮層能在后端形成第二個運(yùn)動和軀體感覺皮層。 33中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性3. Cell differentiationThe process in which a cell take on the appearance and characteristics of a neuron is known as cell differentiation. Differentia

27、tion is the consequence of a specific spatiotemporal pattern of gene expression.Differentiation of the neuroblast into a neuron begins with the appearance of neurites sprouting off the body (all same axon and dendrite at first). The differentiation is programmed well before the neuroblast arrives at

28、 its final resting place. The complexity of dendritic tree is not entirely preprogrammed.The fine structure of axons and dendrites also depends on “environmental” factors in the cortex. 34中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性3.1 Differentiation of cortical areasNiss-stainedposition of the major vibrissae on the facevibriss

29、ae region of S1Barrels in S1- A somatotopic map of the facial vibrissae on mouse cerebral cortex35中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性在決定神經(jīng)細(xì)胞命運(yùn)的過程中，細(xì)胞之間的相互作用起重要作用。這些相互作用既可以發(fā)生于神經(jīng)細(xì)胞與非神經(jīng)細(xì)胞之間，也可以發(fā)生于神經(jīng)細(xì)胞之間；這些相互作用既可以通過彌散在環(huán)境中的誘導(dǎo)因子，也能通過細(xì)胞之間的直接對話。細(xì)胞外的因子最終會在細(xì)胞內(nèi)激活一個特異的分裂和分化程序，使神經(jīng)前體細(xì)胞可以在很大程度上不受環(huán)境的影響，產(chǎn)生不同的神經(jīng)細(xì)胞。通過對這些機(jī)理的進(jìn)一步的研究，發(fā)育神經(jīng)生物學(xué)的最

30、終目標(biāo)是能夠精確地描述：在發(fā)育過程中，不同的神經(jīng)元和膠質(zhì)細(xì)胞如何按準(zhǔn)確的數(shù)量、在特定的時(shí)期、在不同的神經(jīng)系統(tǒng)部位產(chǎn)生。 36中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性 Genesis of connection / synapse formationLM:Model (chemical synapse )Review：definition, classify, structure37中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性EM:38中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性Genesis of connection: for example1. The three phases of pathway formation Pathway s

31、election pathtarget selection structureaddress selection cellThe three phases depends on :Direct cell-to-cell contractcontract between cells and extracellular secretions of other cellcommunication via action potentials and synaptic transmission About 100 billion neurons in brain - remarkably precise

32、 interconnection among them - to perform the functions of the brain.39中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性1. The growing axonThe growing tip of a neurite is called a growth cone, which is specialized to identify an appropriate path for neurite elongation.Structure and feature of growth cone:- probe the environment, moving

33、 in and out of the lamellipodia- takes hold of the substrate and pull the advancing GC forward Growth cone in culture40中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性FasciculationCell adhesion molecules (CAMs)“highway” 41中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性2. Axon guidance and guidance cuesTarget cellExtracecular molecularsSpecial bindingSeconde messenger

34、Function changes of microbubules and actin within growth coneControlling growth cone extendingGuidance cues: chemoattraction and actins concentrate in forepart of a GC chemorepulsion and actins disappear in forepart of a GCMembrane receptors42中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性Chemoattraction and chemorepulsion Netrin sp

35、urs the axon growth toward the midlineThe receptors of Netrin and Slit are be regulated in varying from one side of the midline to other Pushpull Slit chase the axon away the midline43中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性神經(jīng)管沿背腹軸的分化 （A）Shh和BMP家族蛋白分別在脊髓腹側(cè)與背側(cè)形成濃度梯度，從而使神經(jīng)前期細(xì)胞在背腹軸不同的位置選擇不同的命運(yùn)。Shh由脊索和底板分泌，而BMP則由表皮（神經(jīng)管形成之前）或頂板（神經(jīng)

36、管形成之后）分泌。（B）神經(jīng)管沿背腹軸分化的分子模型。Shh抑制I型HD蛋白的表達(dá)，但激活I(lǐng)I型HD蛋白的表達(dá)。I型和II型HD蛋白能抑制彼此的表達(dá)，但它們在腹側(cè)的不同位置有不同的表達(dá)范圍，形成HD蛋白編碼，從而共同分化神經(jīng)前期細(xì)胞，使后者只能產(chǎn)生某一種神經(jīng)元。 44中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性3. Synapse formation- When the growth cone comes in contact with its target, a synapse is formed.- The details of mechanisms of synapse formation in the

37、CNS are still sketchy, - Most of the data comes from studies of the neuromuscular junction. Exp. Steps in the formation of a NMJ: 1. The GMN terminal secretes agrin, (Ca+ entry into the GC triggers neuro- transmitter release and changes in the cytoskeleton adhere to its post- synapse partner) 2. Agr

38、in interacts with MuSK in the muscular cell membrane. 3. The clustering of Ach receptors in the postsynaptic membrane via the action of rapsyn (like a shepherd to gather the receptors at the synapse)Ca+45中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性Nerve growth factor (NGF), a peptide was the first trophic factor tobe identified i

39、n 1940s by Italian biologist Rita Levi-Montalcini.If injecting antibodies of NGF into postsynaptic tissue or axoplasmic transport is disrupted the neurons die. (the work earned levi-montalcini and Cohen the 1986 Nobel Prize)Family members of Neurotrophic Factors include: NGF, NT-3, NT-4 and BDNF (br

40、ain derived neurotrophic factor).PCD is actually a consequence of genetic instructions to self-destruct by a process called apoptosis.46中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性Why dont axon regenerate in our CNS?The critical difference seems tobe the different environments of the CNS and PNS. In the early 1980s, Albert Aguaya

41、 et al. at Montreal General Hospital tested this idea in very important experiment showed as Fig A.Martin Schwab et al. in Zurich university demonstrated that CNS neurons grown in tissue culture extend axons along substrates prepared from Schwann cells but not from oligodendroglia. This finding led

42、to the search for glial factors that inhibit axon growth in the CN, and a molecule called nogo was finally identified early in 2000.Anti-nogo antibody calle IN-1 has been raised, them injected the aitibody into adult rats after spinal cord injury. This treatment enabled about 5%of the severed axons

43、to regenerate Fig A47中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性The elimination of cells and synapseCell death Entire populations of neurons are elimited during pathway formation, a process known as Programmed cell death (PCD). Matching inputs with targets by selective cell death.The input neurons will compete with one another f

44、or limited quantities of trophic factors produced by the target neurons.48中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性2. Changes in synaptic capacityEach neuron can receive on its dendrites and soma a finite number of synapses called synaptic capacity peaks early in development and then declines. Especially in adolescent of macaq

45、ue monkey in visual cortical declined by mostly 50 %, 5000 per second.A useful model system for the study of synaptic elimination: effect of postsynaptic AChR, basal membrane of muscular fibril on neuromuscular synaptic elimination.50中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性Activity-dependent synaptic rearrangement51中樞神經(jīng)系統(tǒng)發(fā)育和其

46、可塑性1. Synaptic segregation (分離)The two input neurons in one eye (top) fire at the same time this is sufficient to cause the top LGN target neuron to fire but not the bottom one. This is the same situation as in part a, except that now the two input neurons in the other eye (bottom) are active simult

47、aneously, causing the bottom target neuron to fire.Over time, neurons that fire together wire together. Notice also that input cells that fire out of sync with the target lose their link.52中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性視頂蓋對應(yīng)投射機(jī)理：頂蓋有內(nèi)高外低的Wnt3梯度，其排斥性受體Ryk在視神經(jīng)呈腹側(cè)高背側(cè)低的梯度，其吸引性受體Fzl均勻分布于視神經(jīng)腹背軸線。 （A）鼻顳視軸突依賴EphA介導(dǎo)的ephrinA排斥

48、信號，EphA以鼻側(cè)高顳側(cè)低的梯度存在于視網(wǎng)膜，而其配體ephrinA以梯度形式存在于頂蓋（B）背腹視軸突投射依賴兩套信號：ephrinB和EphB，Wnt和Ryk，F(xiàn)zl。 ephrinB1在頂蓋內(nèi)呈內(nèi)高外低的梯度，EphB2 和B3在視神經(jīng)呈腹側(cè)高背側(cè)低梯度53中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性Segregation of ocular dominance columns in cat striate contexInitially the inputs from the LGN serving the eyes (different colour) are intermingled in lay

49、er IV. Over the course of fetal and early postnatal development, the inputs from the eyes segregate into ocular dominance columns in layer IV.54中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性Modification of ocular dominance stripes after monocular deprivationA normal monkeyA monkey that had been monocularly deprived for 22 months, starting at 2 weeks of age. The nondeprived eye has been injected, revealing expanded ocular dominance columns in lyer IV. Torsten Wiesel55中樞神經(jīng)系統(tǒng)發(fā)育和其可塑性The ocular do