公募シンポジウム１０：恐怖記憶制御機構解明の新展開
Symposium10 : Cutting edge research to understand mechanisms for regulation of fear memory |
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| 2020/9/11 15:10～15:33 Zoom A
SY10-01
Excitatory mechanisms underlying fear memory valence
*Radulovic Jelena1
1. Northwestern University
*Jelena Radulovic1
1. Northwestern University
The positive or negative value (valence) of past experiences is normally integrated into neuronal circuits that encode episodic memories and plays an important role in guiding behavior. Here we show, using mouse behavioral models, that glutamatergic afferents from the ventral tegmental area to the dorsal hippocampus (VTA→DH) signal negative valence to memory circuits, leading to the formation of fear-inducing context memories and to context-specific reinstatement of fear. To a lesser extent, these projections also contributed to opioid-induced place preference, suggesting a role in signaling positive valence as well, and thus a lack of dedicated polarity. Manipulations of VTA terminal activity weremore effective in females and paralleled by sex differences in glutamatergic signaling. By prioritizing retrieval of negative and positive over neutral memories, the VTA→DH circuit can facilitate the selection of adaptive behaviors when current and past experiences are valence congruent.
| | 2020/9/11 15:33～15:55 Zoom A
SY10-02
想起後の恐怖記憶制御に対する海馬の役割
Roles of hippocampus in fear memory after retrieval
*喜田 聡1
1. 東京大学大学院農学生命科学研究科
*Satoshi Kida1
1. Graduate School of Agriculture and Life Sciences, The University of Tokyo
Memory retrieval is not a passive process. Fear memory retrieval initiates reconsolidation or extinction; reconsolidation maintains or enhances fear memory, while extinction weakens it. We have tried to understand mechanisms for regulation of contextual fear memory after retrieval. We found that reconsolidation of fear memory requires gene expression in the hippocampus, mPFC and amygdala while extinction requires gene expression in the mPFC and amygdala, but not hippocampus. Interestingly, hippocampal gene expression is activated when memory is reconsolidated while this gene expression is inactivated when memory is extinguished. These findings raised the possibility that hippocampal silencing is a crucial step to extinguish fear memory. To investigate this, we examined the function of engrams in the hippocampus using c-fos-tag system and found that inactivation of engram neurons during retrieval erases fear memory by blocking reconsolidation, whereas activation of these engrams during retrieval blocks extinction. These results suggest that modulation of hippocampal fear memory engram cells are crucial processes to determine the fate of memory; reconsolidation or extinction.
| | 2020/9/11 15:55～16:17 Zoom A
SY10-03
レム睡眠中の新生ニューロンによる恐怖記憶制御
Fear memory regulation by adult-born neurons during REM sleep
*坂口 昌徳1、小柳 伊代1、Vergara Pablo1、大庭 彰展1、Srinivasan Sakthivel1、菅谷 佑樹2、Wang Yuteng1、Vogt Kaspar1、Chérasse Yoan1、Kumar Deependra1
1. 筑波大学 国際統合睡眠医科学研究機構、2. 東京大学 神経生理学分野
*Masanori Sakaguchi1, Iyo Koyanagi1, Pablo Vergara1, Akinobu Oba1, Sakthivel Srinivasan1, Yuki Sugaya2, Yuteng Wang1, Kaspar Vogt1, Yoan Chérasse1, Deependra Kumar1
1. Univ. Tsukuba, WPI-IIIS, 2. Univ. Tokyo, Dept. Neurophys.
The occurrence of dreaming during rapid eye movement (REM) sleep prompts interest in the role of REM sleep in hippocampal-dependent episodic memory. Within the mammalian hippocampus, the dentate gyrus (DG) has the unique characteristic of exhibiting neurogenesis persisting into adulthood. Despite their small numbers and sparse activity, adult-born neurons (ABNs) in the DG play critical roles in memory; however, their memory function during sleep is unknown. Here, we investigate whether young ABN activity contributes to memory consolidation during sleep using Ca2+ imaging in freely moving mice. We found that contextual fear learning recruits a population of young ABNs that are reactivated during subsequent REM sleep against a backdrop of overall reduced ABN activity. Optogenetic silencing of this sparse ABN activity during REM sleep alters the structural remodeling of spines on ABN dendrites and impairs memory consolidation. These findings provide a causal link between ABN activity during REM sleep and memory consolidation.
| | 2020/9/11 16:17～16:40 Zoom A
SY10-04
Multi-input synapses, but not LTP-strengthened synapses, correlate with storage of contextual fear memory in aged mice
*Giese Karl Peter1
1. King's College London
*Karl Peter Giese1
1. King's College London
Synaptic changes are the basis of long-term memory storage. Long-term potentiation (LTP), a lasting strengthening of synapses already existing at the time of memory acquisition, is a widely studied memory-storing mechanism. However, long-term memory can also be stored in the absence of LTP. For example, we showed this for pointmutant mice that cannot autophosphorylate the alpha-isoform of calcium/calmodulin-dependent kinase II (CaMKIIalpha). In this mouse model we suggested that generation of two excitatory-input synapses (TES) enables memory storage (Radwanska et al, 2011, PNAS). TES are thought to be generated by the attraction of an additional input onto synapses existing at the time fo training. Recently, we have studied whether in wild-type mice TES generation can also enable memory storage. We found that this could be the case in aged mice (18 month-old). In contrast to young mice, aged mice form memory without structural LTP in hippocampal area CA1 after contextual fear conditioning (CFC). Further, aged mice generated TES after CFC. Accordingly, memory formation in aged, but not young mice is blocked by inhibiting the association of PSD-95 and nNOS, which is required for retrograde signaling to generate TES. Taken together, we suggest that TES generation is a memory mechanism, which predominates in old age to store memory.
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