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“斑馬魚發(fā)育期視網(wǎng)膜興奮性突觸功能的長時程增強”的研究論文。該工作通過運用在體研究方法,，首次發(fā)現(xiàn)了視網(wǎng)膜突觸功能在發(fā)育時期具有長時程增強（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被認為是動物學(xué)習(xí)/記憶和發(fā)育過程中經(jīng)驗依賴性的神經(jīng)環(huán)路修飾的突觸機制之一,。盡管大量的研究已發(fā)現(xiàn),，在發(fā)育時期，視覺經(jīng)驗和神經(jīng)活動對于視網(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迷,。
該工作以斑馬魚為模式動物，利用在體全細胞電生理和在體雙光子成像等技術(shù),，在整體動物上研究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天的斑馬魚上,，高頻電脈沖刺激能夠在視網(wǎng)膜雙極細胞（bipolar cell）到神經(jīng)節(jié)細胞（retinal ganglion cell）這一級興奮性突觸上誘導(dǎo)LTP,，而在15 - 20天的動物上則不能；該LTP的誘導(dǎo)需要突觸后NMDA受體的激活,。其次,，該LTP的表達涉及突觸前的變化，包括雙極細胞軸突末端鈣反應(yīng)的長時程增加,；微小興奮性突觸后電流（mEPSC）頻率的增加,；突觸后電流的配對脈沖比率（PPR）及變異系數(shù)（CV）的降低等。藥理實驗表明這些突觸前的變化主要由突觸逆向信號分子花生四烯酸（arachidonic acid）介導(dǎo),。進一步的功能實驗發(fā)現(xiàn),，重復(fù)的光刺激也能在同一級突觸上誘導(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)細胞的對光反應(yīng),。該工作首次闡明了LTP的確存在于發(fā)育時期的視網(wǎng)膜中,，為視覺經(jīng)驗引起的視覺神經(jīng)環(huán)路修飾和發(fā)育提供了突觸機制。
該研究工作受到科技部“973”和重大科學(xué)研究計劃,、中國科學(xué)院“百人計劃”,、以及上海市科委“浦江人才”計劃和基礎(chǔ)研究重大項目等基金資助。（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.
