Neuron雜志于8月9日發(fā)表了上海生科院神經(jīng)科學(xué)研究所杜久林研究組題為“斑馬魚(yú)發(fā)育期視網(wǎng)膜興奮性突觸功能的長(zhǎng)時(shí)程增強(qiáng)”的研究論文,。該工作通過(guò)運(yùn)用在體研究方法,，首次發(fā)現(xiàn)了視網(wǎng)膜突觸功能在發(fā)育時(shí)期具有長(zhǎng)時(shí)程增強(qiáng)（long-term potentiation, LTP）的能力。該工作主要由博士生魏宏平等在杜久林研究員的指導(dǎo)下完成,。
LTP被認(rèn)為是動(dòng)物學(xué)習(xí)/記憶和發(fā)育過(guò)程中經(jīng)驗(yàn)依賴(lài)性的神經(jīng)環(huán)路修飾的突觸機(jī)制之一,。盡管大量的研究已發(fā)現(xiàn)，在發(fā)育時(shí)期,，視覺(jué)經(jīng)驗(yàn)和神經(jīng)活動(dòng)對(duì)于視網(wǎng)膜神經(jīng)環(huán)路的形成至關(guān)重要,，但LTP在視網(wǎng)膜中是否存在還是個(gè)迷。
該工作以斑馬魚(yú)為模式動(dòng)物,，利用在體全細(xì)胞電生理和在體雙光子成像等技術(shù),，在整體動(dòng)物上研究LTP是否存在于發(fā)育期的視網(wǎng)膜。首先,，作者發(fā)現(xiàn)在出生后3 - 6天的斑馬魚(yú)上,，高頻電脈沖刺激能夠在視網(wǎng)膜雙極細(xì)胞（bipolar cell）到神經(jīng)節(jié)細(xì)胞（retinal ganglion cell）這一級(jí)興奮性突觸上誘導(dǎo)LTP,，而在15 - 20天的動(dòng)物上則不能,；該LTP的誘導(dǎo)需要突觸后NMDA受體的激活。其次,，該LTP的表達(dá)涉及突觸前的變化,，包括雙極細(xì)胞軸突末端鈣反應(yīng)的長(zhǎng)時(shí)程增加；微小興奮性突觸后電流（mEPSC）頻率的增加；突觸后電流的配對(duì)脈沖比率（PPR）及變異系數(shù)（CV）的降低等,。藥理實(shí)驗(yàn)表明這些突觸前的變化主要由突觸逆向信號(hào)分子花生四烯酸（arachidonic acid）介導(dǎo),。進(jìn)一步的功能實(shí)驗(yàn)發(fā)現(xiàn)，重復(fù)的光刺激也能在同一級(jí)突觸上誘導(dǎo)LTP,，并且由電刺激和不同種模式的光刺激誘導(dǎo)產(chǎn)生的LTP都能有效增加神經(jīng)節(jié)細(xì)胞的對(duì)光反應(yīng),。該工作首次闡明了LTP的確存在于發(fā)育時(shí)期的視網(wǎng)膜中，為視覺(jué)經(jīng)驗(yàn)引起的視覺(jué)神經(jīng)環(huán)路修飾和發(fā)育提供了突觸機(jī)制,。
該研究工作受到科技部“973”和重大科學(xué)研究計(jì)劃,、中國(guó)科學(xué)院“百人計(jì)劃”、以及上海市科委“浦江人才”計(jì)劃和基礎(chǔ)研究重大項(xiàng)目等基金資助,。（生物谷bioon.com）
doi:10.1016/j.neuron.2012.05.031
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Activity-Induced Long-Term Potentiation of Excitatory Synapses in Developing Zebrafish Retina In Vivo
Activity-Induced Long-Term Potentiation of Excitatory Synapses in Developing Zebrafish Retina In Vivo
Neural activity-induced long-term potentiation (LTP) of synaptic transmission is believed to be one of the cellular mechanisms underlying experience-dependent developmental refinement of neural circuits. Although it is well established that visual experience and neural activity are critical for the refinement of retinal circuits, whether and how LTP occurs in the retina remain unknown. Using in vivo perforated whole-cell recording and two-photon calcium imaging, we find that both repeated electrical and visual stimulations can induce LTP at excitatory synapses formed by bipolar cells on retinal ganglion cells in larval but not juvenile zebrafish. LTP induction requires the activation of postsynaptic N-methyl-D-aspartate receptors, and its expression involves arachidonic acid-dependent presynaptic changes in calcium dynamics and neurotransmitter release. Physiologically, both electrical and visual stimulation-induced LTP can enhance visual responses of retinal ganglion cells. Thus, LTP exists in developing retinae with a presynaptic locus and may serve for visual experience-dependent refinement of retinal circuits.
