美國(guó)猶他大學(xué)James G. Heys研究組在研究中取得進(jìn)展。他們發(fā)現(xiàn)內(nèi)側(cè)內(nèi)嗅皮層（MEC）介導(dǎo)環(huán)境依賴性間隔計(jì)時(shí)行為。2024年6月14日，國(guó)際學(xué)術(shù)期刊《自然-神經(jīng)科學(xué)》發(fā)表了這一成果。
研究人員表示，情節(jié)記憶需要對(duì)經(jīng)驗(yàn)時(shí)間結(jié)構(gòu)進(jìn)行編碼，并依賴于內(nèi)側(cè)顳葉大腦回路，包括MEC。最近的研究發(fā)現(xiàn)了內(nèi)側(cè)顳葉皮層的 "時(shí)間細(xì)胞"，這些細(xì)胞在完成時(shí)間間隔計(jì)時(shí)任務(wù)時(shí)會(huì)在特定時(shí)刻發(fā)射信號(hào)，并覆蓋整個(gè)計(jì)時(shí)周期。有人推測(cè)，MEC時(shí)間細(xì)胞可提供外顯記憶所需的時(shí)間信息，然而，目前仍不得而知它們是否表現(xiàn)出編碼不同時(shí)間背景所需的學(xué)習(xí)動(dòng)力。
為了探索MEC時(shí)間細(xì)胞的工作模式，研究人員開(kāi)發(fā)了一種新的行為實(shí)驗(yàn)，要求小鼠區(qū)分時(shí)間情境。結(jié)合細(xì)胞分辨率鈣成像方法，研究發(fā)現(xiàn)MEC時(shí)間細(xì)胞顯示出與任務(wù)學(xué)習(xí)相關(guān)的神經(jīng)活動(dòng)。通過(guò)化學(xué)失活，研究發(fā)現(xiàn)MEC活動(dòng)是學(xué)習(xí)情境依賴性時(shí)間間隔行為所必需的。
最后，研究發(fā)現(xiàn)了一種共同的電路機(jī)制，它可以驅(qū)動(dòng)MEC中時(shí)間細(xì)胞和空間選擇性神經(jīng)元的序列活動(dòng)。該研究表明，MEC時(shí)間細(xì)胞的時(shí)鐘樣發(fā)射可通過(guò)學(xué)習(xí)進(jìn)行調(diào)節(jié)，從而跟蹤通過(guò)經(jīng)驗(yàn)產(chǎn)生的各種時(shí)間結(jié)構(gòu)。
附：英文原文
Title: Medial entorhinal cortex mediates learning of context-dependent interval timing behavior
Author: Bigus, Erin R., Lee, Hyun-Woo, Bowler, John C., Shi, Jiani, Heys, James G.
Issue&Volume: 2024-06-14
Abstract: Episodic memory requires encoding the temporal structure of experience and relies on brain circuits in the medial temporal lobe, including the medial entorhinal cortex (MEC). Recent studies have identified MEC ‘time cells’, which fire at specific moments during interval timing tasks, collectively tiling the entire timing period. It has been hypothesized that MEC time cells could provide temporal information necessary for episodic memories, yet it remains unknown whether they display learning dynamics required for encoding different temporal contexts. To explore this, we developed a new behavioral paradigm requiring mice to distinguish temporal contexts. Combined with methods for cellular resolution calcium imaging, we found that MEC time cells display context-dependent neural activity that emerges with task learning. Through chemogenetic inactivation we found that MEC activity is necessary for learning of context-dependent interval timing behavior. Finally, we found evidence of a common circuit mechanism that could drive sequential activity of both time cells and spatially selective neurons in MEC. Our work suggests that the clock-like firing of MEC time cells can be modulated by learning, allowing the tracking of various temporal structures that emerge through experience.
DOI: 10.1038/s41593-024-01683-7
Source: https://www.nature.com/articles/s41593-024-01683-7
期刊信息
Nature Neuroscience：《自然—神經(jīng)科學(xué)》，創(chuàng)刊于1998年。隸屬于施普林格·自然出版集團(tuán)，最新IF：28.771
官方網(wǎng)址：https://www.nature.com/neuro
投稿鏈接：https://mts-nn.nature.com/cgi-bin/main.plex
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