本文選題：視網(wǎng)膜波 + ON-OFF系統(tǒng)　； 參考：《天津醫(yī)科大學(xué)》2013年博士論文

【摘要】：研究目的研究哺乳動(dòng)物早期視覺發(fā)育期間谷氨酸能視網(wǎng)膜波對(duì)視網(wǎng)膜內(nèi)ON、OFF系統(tǒng)分離修飾作用的突觸特點(diǎn)及突觸機(jī)制。研究方法1.采用生后8天和生后10-12天的ChAT-Cre-GCamp3小鼠視網(wǎng)膜,觀察對(duì)比ON、OFF ChAT-band的鈣依賴性電活動(dòng)在第二、三視網(wǎng)膜波階段的特點(diǎn)和差異;2.采用生后10-12天的ChAT-Cre-Tdtomato小鼠,應(yīng)用全細(xì)胞雙膜片鉗技術(shù),觀察第三階段視網(wǎng)膜波ON、OFF SAC在電壓鉗模式下興奮性突觸輸入的時(shí)空模式的特點(diǎn),比較時(shí)間模式的差異;3.應(yīng)用藥理學(xué)方法觀察相關(guān)受體或通道對(duì)第三階段視網(wǎng)膜波ON、OFF SAC時(shí)間模式的影響;4.應(yīng)用膜片鉗全細(xì)胞記錄技術(shù)結(jié)合光遺傳學(xué)方法,使用藍(lán)色LED光源特異性激活mGluR6-ChannelRhodopsin-2小鼠視網(wǎng)膜ON雙極細(xì)胞,觀察ON系統(tǒng)的激活對(duì)不同類型神經(jīng)節(jié)細(xì)胞的作用,結(jié)合藥理學(xué)方法探討可能的突觸機(jī)制。研究結(jié)果1.ON、OFF ChAT-band的自發(fā)性鈣依賴性電活動(dòng)的時(shí)間模式在第二階段視網(wǎng)膜波時(shí)期呈現(xiàn)同步化,在第三階段視網(wǎng)膜波時(shí)期呈現(xiàn)非同步化,且遵循特定的時(shí)間順序即ON在OFF之前,時(shí)間差異為743.31±190.75ms(n=4 retina,25 waves)。2.第三階段視網(wǎng)膜波在ON、OFF SAC中發(fā)生的起始時(shí)間相對(duì)一致但呈現(xiàn)主波和副波兩個(gè)波形:ON SAC為一大一小即主波在前副波在后,OFF SAC為一小一大,副波在前主波在后。主波波峰出現(xiàn)的時(shí)間在ON、OFF兩個(gè)SAC中呈現(xiàn)非同步化,但遵循一個(gè)特定規(guī)律:即每次ON SAC的主波波峰的出現(xiàn)時(shí)間都先于OFF SAC,時(shí)間差為829.85±282.78(n=14 pairs);并且ON SAC的主波與OFF SAC的副波對(duì)應(yīng)、ON SAC的副波與OFF SAC的主波對(duì)應(yīng),有相對(duì)一致的起始和結(jié)束時(shí)間。3.第三階段ON GC視網(wǎng)膜波的起始時(shí)間、波形都和ON SAC大致吻合;OFF GC則和OFF SAC類似,OFF GC主波波峰在ON SAC之后,表現(xiàn)出和ON、OFF SAC相似的時(shí)間差異;ON-OFF GC則有兩個(gè)主波,第一個(gè)主波和ON SAC的主波基本重合,第二個(gè)主波緊跟其后。4.甘氨酸能受體阻滯劑STR可以同步化第三階段視網(wǎng)膜波ON、OFF SAC時(shí)間模式,STR聯(lián)合GABA受體阻滯劑PTX可以起到協(xié)同作用,單純PTX、縫隙連接阻滯劑18-betaGA不能改變ON、OFF SAC非同步化模式。5.單純激活ON雙極細(xì)胞可以誘發(fā)神經(jīng)節(jié)細(xì)胞"視網(wǎng)膜波樣"的反應(yīng):ON神經(jīng)節(jié)細(xì)胞在ChR2反應(yīng)結(jié)束后出現(xiàn)一個(gè)類似于副波的小波;OFF神經(jīng)節(jié)細(xì)胞則在ON型雙極細(xì)胞被激活時(shí),受到某種抑制作用,表現(xiàn)為較小水平的去極化形成類似于副波的小波,當(dāng)ChR2反應(yīng)結(jié)束后,出現(xiàn)一個(gè)類似主波的反應(yīng)幅度較大的波;ON-OFF GC表現(xiàn)為兩個(gè)主波的雙相波形。ON、OFF、ON-OFF RGC在ChR2反應(yīng)結(jié)束后所誘發(fā)的內(nèi)向電流可以被STR阻斷。研究結(jié)論1.視網(wǎng)膜ON、OFF系統(tǒng)的修飾作用始于視網(wǎng)膜波第三階段。在視網(wǎng)膜內(nèi)ON、OFF系統(tǒng)各自獨(dú)立的通路結(jié)構(gòu)已經(jīng)形成的基礎(chǔ)上,視網(wǎng)膜波的興奮性遞質(zhì)從乙酰膽堿過渡到谷氨酸,視網(wǎng)膜波對(duì)視網(wǎng)膜內(nèi)ON、OFF系統(tǒng)的修飾作用才會(huì)啟動(dòng)。2.第三階段視網(wǎng)膜波能夠?qū)σ暰W(wǎng)膜內(nèi)ON、OFF細(xì)胞進(jìn)行非同步化修飾,這種修飾作用不僅作用于輸出細(xì)胞還作用于輸出細(xì)胞上游的中間神經(jīng)元。3.ON、OFF細(xì)胞在第三階段視網(wǎng)膜波期間表現(xiàn)出不同的時(shí)間模式和空間模式。這種時(shí)空差異由突觸前機(jī)制所介導(dǎo)。4.視網(wǎng)膜波通過隨機(jī)的、反復(fù)的、轉(zhuǎn)換神經(jīng)遞質(zhì)等方式使相同類型輸出細(xì)胞同步化,不同類型輸出細(xì)胞先后經(jīng)歷同步化與非同步化,對(duì)視網(wǎng)膜向高級(jí)視覺中樞的輸出進(jìn)行修飾、重塑與改建以引導(dǎo)高級(jí)中樞內(nèi)在視覺發(fā)生以前視覺環(huán)路的精確修飾。5.在阻斷了抑制性神經(jīng)遞質(zhì)γ-氨基丁酸和甘氨酸傳遞后,來自O(shè)N、OFF雙極細(xì)胞的興奮性驅(qū)動(dòng)是同步化的。甘氨酸對(duì)第三階段視網(wǎng)膜ON、OFF系統(tǒng)分離起重要調(diào)控作用。6.第三階段視網(wǎng)膜波時(shí)期,ON雙極細(xì)胞通過甘氨酸能抑制性通路抑制OFF雙極細(xì)胞的興奮性釋放,繼而產(chǎn)生ON、OFF細(xì)胞反應(yīng)的非同步化。
[Abstract]:The purpose of this study is to investigate the synaptic characteristics and synaptic mechanism of the effects of glutamic acid energy retinal waves on the ON and OFF system during early visual development in mammals. Methods 1. the study was performed on the retina of ChAT-Cre-GCamp3 mice at 8 days after birth and 10-12 days after birth, and the calcium dependent electrical activity of ON and OFF ChAT-band was second, Three the characteristics and differences of the stage of retina wave; 2. the ChAT-Cre-Tdtomato mice of 10-12 days after birth were used to observe the characteristics of the temporal and spatial patterns of the excitatory synaptic input in the third stage retina wave ON, OFF SAC under the voltage clamp mode, and compared the difference of time mode. 3. the application of pharmacological methods to observe the related receptors The influence of the channel on the third stage retinal wave ON, OFF SAC time pattern; 4. using the patch clamp whole cell recording technique combined with the photo genetics method, using the blue LED light source to activate the mGluR6-ChannelRhodopsin-2 mouse retinal ON bipolar cells specifically, to observe the effect of the activation of the ON system on the different types of ganglion cells, and to combine the pharmacology with the pharmacology of the ON system. Study methods explore possible synaptic mechanisms. Results 1.ON, OFF ChAT-band of spontaneous calcium dependent electrical activity synchronization in the second stage of the retinal wave period, in the third stage of the retinal wave period is non synchronous, and follow the specific time order that ON before OFF, the time difference is 743.31 + 190.75ms (n=4 Retina, 25 waves) the onset time of retinal waves in the.2. third stage is relatively consistent in the onset time of ON, OFF SAC, but presents two waveforms of the main wave and the secondary wave: ON SAC is a big one, that is, after the main wave is in the front side wave, the OFF SAC is a small one, the secondary wave is in the front of the main wave. The time of the main wave peak appears in ON, and the two OFF of OFF are non synchronous, but the time of the main wave peak is in ON. The time difference between the main wave peak of each ON SAC is preceded to OFF SAC, the time difference is 829.85 + 282.78 (n=14 pairs), and the main wave of ON SAC corresponds to the auxiliary wave of OFF SAC, and the secondary wave of ON SAC is corresponding to the main wave. Between the ON SAC and the OFF SAC, the OFF GC is similar to the OFF SAC, and the OFF GC main wave peak appears after ON SAC, showing a similar time difference between ON and OFF; the first main wave is basically coincided with the main wave of the primary wave and the main wave, and the third step can be synchronized with the glycine receptor blocker after the second main waves. Retina wave ON, OFF SAC time pattern, STR combined with GABA receptor blocker PTX can play a synergistic role, pure PTX, gap junction blocker 18-betaGA can not change ON, OFF SAC non synchronous mode.5. only activate bipolar cells can induce ganglion cell "retina wave like" response: ganglion cells after the end of the reaction out of the reaction A wavelet similar to the secondary wave is present; OFF ganglion cells are suppressed when ON type bipolar cells are activated, showing a small level of depolarization to form a wavelet similar to the vice wave. When the ChR2 reaction ends, a larger wave similar to the main wave is found; ON-OFF GC shows a dual phase waveform of two main waves.O. The introverted current induced by N, OFF, ON-OFF RGC can be blocked by STR after the end of ChR2 reaction. Conclusion 1. retina ON, the modification of OFF system begins at the third stage of retina wave. On the basis of the formation of the independent pathway structure of the ON in the retina, the excitatory transmitters of the omentum waves transition from acetylcholine to the valley. The modification of retina, retina wave to the ON, OFF system in the retina will initiate the.2. third stage of retinal waves to be able to unsynchronize the ON, OFF cells in the retina, which not only acts on the output cells but also acts on the intermediate deity.3.ON in the upstream of the output cell, and the OFF cell during the third stage of the retina wave. There are different time patterns and spatial patterns. This spatio-temporal difference is mediated by the presynaptic mechanism of.4. retina waves to synchronize the same type of output cells through random, repeated, and converted neurotransmitters, and the output of different types of cells successively experience synchronization and asynchronization, and the output of the retina to the advanced visual center. Modified, reshaped and remodeled to guide the precise modification of the visual loop prior to the inherent visual occurrence of the advanced center.5., after blocking the inhibitory neurotransmitters gamma aminobutyric acid and glycine transfer, the excitatory drive from ON, OFF bipolar cells is synchronized. Glycine plays an important role in the separation of the third stage retinal ON, OFF system. During the.6. third stage of the retina wave period, ON bipolar cells inhibit the excitatory release of OFF bipolar cells through the glycine inhibitory pathway, and then produce ON, OFF cell reaction asynchrony.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2013
【分類號(hào)】：R774.1

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4 劉t熡，

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