透過鈣離子成像技術探尋腹側海馬迴於睡眠時對於恐懼記憶 提取所扮演之角色

Identify the role of ventral hippocampus in fear memory retrieval during sleep through calcium imaging

張晉源(Ching-Yuan Chang)

指導教授 ： 蕭逸澤

國立臺灣大學/獸醫專業學院/獸醫學研究所/碩士(2021年)

https://doi.org/10.6342/NTU202103225

摘要

長久以來，海馬迴一直都被認為是固化記憶的中心腦區，而許多研究更進一步指出它在恐懼記憶的再提取或是情境式恐懼的習得中扮演重要的角色。不過整體而言，這些研究幾乎都是在老鼠清醒的階段所進行的，對於海馬迴是否在睡眠時參與恐懼記憶的再提取便不得而知。為了驗證海馬迴是否參與睡眠時恐懼記憶的再提取，我們選擇使用鈣離子成像的技術搭配微型顯微攝影機來進行實驗，因為這些技術的好處是可以讓我們即時監控活體內腹側海馬迴神經細胞的活性。
我們的研究指出，在恐懼制約後播放提示音會使腹側海馬迴整體的神經活性上升，說明了此腦區大多數的神經細胞應參與了恐懼記憶被提取後的再固化反應;此外，在恐懼記憶被再度提取時，腹側海馬迴的神經元大致上可以依不同功能劃分成不同類別，並在該期間扮演不同的角色。在這群神經元中，有兩群神經細胞對於提示音相當敏感，分別是我們所定義的“Tone cells”以及“Tone-negative cells”; 而不論是這兩群神經的細胞活性或是與周邊神經的同步性，它們的浮動都與提示音出現的時間點都有著高度相關。這些結果指出這些對聲音極度敏感的細胞很有可能有能力帶動周圍神經群集的活性以及同步性，進而決定這些被再提取的恐懼記憶的命運：再固化，抑或是去穩定。

關鍵字

腹側海馬迴 ； 鈣離子成像 ； 睡眠 ； 恐懼記憶

並列摘要

Hippocampus has long been regarded as a memory-consolidating center, and there are numerous researches further indicate the important role in fear memory retrieval and contextual fear learning. In general, experiments of these researches are mostly conducted on the sober stage of mice; however, whether the hippocampus involving in the retrieval of fear memory during sleep remains unknown. Here, we used calcium imaging and miniaturized microscope (miniscope), which enable us to observe the real-time neural activity in vivo, for monitoring whether ventral hippocampal neurons participating in fear memory retrieval during sleep or not.
First of all, the elevating activity level of vCA1 neurons was noted after the cue tone appeared in those fear-conditioned mice, meaning that most of these neurons may contribute to the reconsolidation process after fear memory retrieval during sleep. Furthermore, our study reveals that these neurons can be subdivided into several kinds of cells depending on their function. Among these neurons, two populations are highly associated with the cue tone, respectively tone cells and tone-negative cells, exhibiting extremely corresponding fluctuation of neural activity and synchronization to the cue tone. These findings suggest that those tone-sensitive cells may probably drive the synchronization of neural ensembles, eventually lead the retrieved memory to completely different destinies: reconsolidation or destabilization.

並列關鍵字

ventral hippocampus ； fear memory ； retrieval ； calcium imaging ； sleep

參考文獻

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