7月1日,中科院上海生科院神經(jīng)所郭愛克研究組在PNAS雜志發(fā)表一篇文章,，該文章的研究工作引入了一種新的雙色鈣成像方法，并利用這種方法對(duì)果蠅中單個(gè)蘑菇體神經(jīng)元對(duì)嗅覺刺激的反應(yīng)特性是如何由前級(jí)的投射神經(jīng)元轉(zhuǎn)換而來(lái)進(jìn)行了探討,。
在絕大多數(shù)情況下,，單個(gè)神經(jīng)元從許多突觸前神經(jīng)元接收輸入，并將這些輸入信號(hào)整合為單一的輸出信號(hào),。所以,，單個(gè)神經(jīng)元對(duì)外界刺激的反應(yīng)特性在很大程度上是由它所接收的突觸前神經(jīng)元的反應(yīng)特性所轉(zhuǎn)換而來(lái)的。如果能夠?qū)⒁粋€(gè)神經(jīng)元所接收的突觸前神經(jīng)元的反應(yīng)特性逐一測(cè)量出來(lái),，并和這個(gè)神經(jīng)元自身的反應(yīng)特性進(jìn)行比較,，就可以對(duì)這個(gè)神經(jīng)元所參與的環(huán)路計(jì)算得到清晰的了解。然而,，由于神經(jīng)環(huán)路的結(jié)構(gòu)極端復(fù)雜,，迄今為止尚沒有一種有效的策略能夠?qū)⒛骋簧窠?jīng)元的突觸前神經(jīng)元逐一找出，并進(jìn)行詳細(xì)的功能研究,。
為了解決這個(gè)問題,，郭愛克研究組引入了一種基于雙色鈣成像的新策略，并將其應(yīng)用于果蠅的蘑菇體神經(jīng)元（KC）上,。作者們用綠色鈣指示蛋白G-CaMP標(biāo)出單個(gè)KC,，同時(shí)用紅色鈣指示蛋白R(shí)-GECO標(biāo)出許多前級(jí)的投射神經(jīng)元（PN）；通過結(jié)構(gòu)上的追蹤,，就可以分辨出單個(gè)KC從哪些PN軸突末梢接收輸入,，并用功能成像將這個(gè)KC和它所接收的PN軸突末梢對(duì)氣味的反應(yīng)逐一測(cè)量出來(lái)。
使用這種策略,，作者們發(fā)現(xiàn)單個(gè)KC對(duì)氣味的反應(yīng)選擇性在很大程度上可以從它所接收的PN軸突末梢的氣味反應(yīng)進(jìn)行預(yù)測(cè),。只要將這些PN軸突末梢的氣味反應(yīng)進(jìn)行線性相加，并對(duì)所得到的結(jié)果和預(yù)先設(shè)定的閾值進(jìn)行比較,，就可以較為精確的預(yù)測(cè)單個(gè)KC對(duì)哪些氣味起反應(yīng),。這說明KC對(duì)氣味的反應(yīng)選擇性主要是由其接收的突觸前PN的反應(yīng)特性所決定的。即使某一氣味不能激活KC的輸出,，也經(jīng)?？梢栽谠揔C的樹突上觀察到空間上局限于突觸后位點(diǎn)的鈣反應(yīng),。這種局部鈣反應(yīng)很可能對(duì)應(yīng)于單個(gè)PN軸突末梢的激活在KC中所引起的閾下興奮性突觸后電位。單個(gè)局部鈣反應(yīng)的大小和其相應(yīng)的突觸前PN軸突末梢的鈣反應(yīng)大小經(jīng)常具有線性相關(guān)性,，使作者們得以對(duì)單個(gè)突觸位點(diǎn)進(jìn)行突觸強(qiáng)度的測(cè)量,。另外，單個(gè)KC所接收的PN軸突末梢的數(shù)目和這些PN-KC突觸的平均強(qiáng)度具有反相關(guān)的關(guān)系,。
這項(xiàng)工作所引入的策略對(duì)果蠅蘑菇體中的信息傳遞和整合的過程提供了一種全新的視角,，并一定程度上揭示了蘑菇體神經(jīng)元?dú)馕毒幋a特性的來(lái)源。在未來(lái),，這種策略有可能應(yīng)用于其它多種環(huán)路,，以揭示更加復(fù)雜的神經(jīng)元反應(yīng)特性是如何產(chǎn)生的。
該課題由博士研究生李昊,、李怡明,、雷正昶、王開宇在郭愛克研究員指導(dǎo)下完成,。課題受科技部973項(xiàng)目,、國(guó)家自然科學(xué)基金、中國(guó)科學(xué)院戰(zhàn)略性先導(dǎo)科技專項(xiàng)（B類）“腦功能聯(lián)結(jié)圖譜計(jì)劃”等資助,，在中科院神經(jīng)科學(xué)研究所獨(dú)立完成,。（生物谷 Bioon.com）
生物谷推薦的英文摘要
PNAS 10.1073/pnas.1305857110
Transformation of odor selectivity from projection neurons to single mushroom body neurons mapped with dual-color calcium imaging
Hao Li, Yiming Li, Zhengchang Lei, Kaiyu Wang, and Aike Guo
Although the response properties of most neurons are, to a large extent, determined by the presynaptic inputs that they receive, comprehensive functional characterization of the presynaptic inputs of a single neuron remains elusive. Toward this goal, we introduce a dual-color calcium imaging approach that simultaneously monitors the responses of a single postsynaptic neuron together with its presynaptic axon terminal inputs in vivo. As a model system, we applied the strategy to the feed-forward connections from the projection neurons (PNs) to the Kenyon cells (KCs) in the mushroom body of Drosophila and functionally mapped essentially all PN inputs for some of the KCs. We found that the output of single KCs could be well predicted by a linear summation of the PN input signals, indicating that excitatory PN inputs play the major role in generating odor-selective responses in KCs. When odors failed to activate KC output, local calcium transients restricted to individual postsynaptic sites could be observed in the KC dendrites. The response amplitudes of the local transients often correlated linearly with the presynaptic response amplitudes, allowing direct assay of the strength of single synaptic sites. Furthermore, we found a scaling relationship between the total number of PN terminals that a single KC received and the average synaptic strength of these PN-KC synapses. Our strategy provides a unique perspective on the process of information transmission and integration in a model neural circuit and may be broadly applicable for the study of the origin of neuronal response properties.
