1月18日,，美國(guó)物理學(xué)家組織網(wǎng)報(bào)道,，美國(guó)科學(xué)家繪制出了迄今最完整的大腦神經(jīng)相互作用以增強(qiáng)從學(xué)習(xí)到服藥等行為的圖譜，有望為科學(xué)家們治療成癮開(kāi)辟新道路,。相關(guān)研究發(fā)表在1月18日出版的《自然》雜志上,。
哈佛大學(xué)分子和細(xì)胞生物學(xué)副教授瑙石哥·烏騏達(dá)領(lǐng)導(dǎo)的科研團(tuán)隊(duì)，在多年研究名為獎(jiǎng)賞預(yù)測(cè)失誤的腦部活動(dòng)過(guò)程中得到了上述結(jié)果,。此前,，科學(xué)家們認(rèn)為，預(yù)測(cè)失誤是學(xué)習(xí)的關(guān)鍵組成部分,，也是巴胺神經(jīng)元放電以對(duì)一個(gè)意想不到的“獎(jiǎng)賞”做出反應(yīng)以增強(qiáng)導(dǎo)致這種報(bào)償行為的產(chǎn)物,。
但烏騏達(dá)和哈佛大學(xué)以及貝斯以色列女執(zhí)事醫(yī)療中心的同事在最新研究中卻指出，“獎(jiǎng)賞”預(yù)測(cè)失誤實(shí)際上是兩類(lèi)神經(jīng)元(一種依靠多巴胺的神經(jīng)元以及一種使用神經(jīng)傳遞素GABA的抑制性神經(jīng)元)之間復(fù)雜相互作用的產(chǎn)物,。烏騏達(dá)表示：“此前,，人們都不知道GABA神經(jīng)元與獎(jiǎng)賞和懲罰循環(huán)有何關(guān)系。我們的最新研究表明,，GABA神經(jīng)元抑制了多巴胺神經(jīng)元,，它們雙管齊下來(lái)計(jì)算獎(jiǎng)賞失誤。”
研究多巴胺或GABA神經(jīng)元面臨的挑戰(zhàn)在于,，這兩種細(xì)胞會(huì)相互混合進(jìn)入大腦內(nèi)一個(gè)比較小的區(qū)域,，使研究人員很難確切地知道他們正在觀察的是哪種細(xì)胞，烏騏達(dá)團(tuán)隊(duì)最終找到了巧妙的辦法解決了這一難題。
科學(xué)家們對(duì)老鼠的兩組神經(jīng)元(一組用于研究多巴胺神經(jīng)元,；一組用于研究GABA神經(jīng)元)進(jìn)行了遺傳修改,，使得當(dāng)這些神經(jīng)元被激光脈沖照射時(shí)會(huì)放電，一旦研究人員確定他們正在測(cè)量正確類(lèi)型的神經(jīng)元,，他們就使用電極來(lái)測(cè)量這些神經(jīng)元是否放電以及什么時(shí)候會(huì)放電以對(duì)期望的以及實(shí)際的獎(jiǎng)賞做出反應(yīng),。結(jié)果表明，當(dāng)多巴胺神經(jīng)元放電發(fā)出獎(jiǎng)賞預(yù)測(cè)失誤信號(hào)時(shí),，GABA神經(jīng)元會(huì)發(fā)出一個(gè)期望的獎(jiǎng)賞信號(hào),。因此，GABA神經(jīng)元幫助多巴胺神經(jīng)元計(jì)算獎(jiǎng)賞預(yù)測(cè)失誤,。
烏騏達(dá)表示,，這項(xiàng)研究發(fā)現(xiàn)非常重要，因?yàn)樗屛覀兛梢圆捎萌碌慕嵌葋?lái)理解如何對(duì)行為進(jìn)行強(qiáng)化或者通過(guò)正常的腦部功能,；或者通過(guò)破壞這兩類(lèi)神經(jīng)元相互作用的方式,。烏騏達(dá)說(shuō)：“這是一種新的看待成癮的方式?；谶@一理論,，我們能研發(fā)出新的治療成癮的理論。”（生物谷 Bioon.com）
doi:10.1038/nature10754
PMC:
PMID:
Neuron-type-specific signals for reward and punishment in the ventral tegmental area
Jeremiah Y. Cohen,, Sebastian Haesler,Linh Vong, Bradford B. Lowell & Naoshige Uchida
Dopamine has a central role in motivation and reward. Dopaminergic neurons in the ventral tegmental area (VTA) signal the discrepancy between expected and actual rewards (that is, reward prediction error), but how they compute such signals is unknown. We recorded the activity of VTA neurons while mice associated different odour cues with appetitive and aversive outcomes. We found three types of neuron based on responses to odours and outcomes: approximately half of the neurons (type I, 52%) showed phasic excitation after reward-predicting odours and rewards in a manner consistent with reward prediction error coding; the other half of neurons showed persistent activity during the delay between odour and outcome that was modulated positively (type II, 31%) or negatively (type III, 18%) by the value of outcomes. Whereas the activity of type I neurons was sensitive to actual outcomes (that is, when the reward was delivered as expected compared to when it was unexpectedly omitted), the activity of type II and type III neurons was determined predominantly by reward-predicting odours. We ‘tagged’ dopaminergic and GABAergic neurons with the light-sensitive protein channelrhodopsin-2 and identified them based on their responses to optical stimulation while recording. All identified dopaminergic neurons were of type I and all GABAergic neurons were of type II. These results show that VTA GABAergic neurons signal expected reward, a key variable for dopaminergic neurons to calculate reward prediction error.
