公募シンポジウム１：記憶痕跡細胞の多様性と多能性
Symposium1 : Functional diversity and multipotency of memory engram cells |
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| 2020/9/10 9:00～9:20 Zoom B
SY1-01
古い記憶想起における海馬歯状回記憶痕跡細胞の関与
Contribution of the memory-trace ensemble in the dentate gyrus to remote memory recall
*奥野 浩行1
1. 鹿児島大学大学院医歯学総合研究科
*Hiroyuki Okuno1
1. Graduate School of Medical and Dental Sciences, Kagoshima University
The hippocampus, including the dentate gyrus (DG), is crucial for spatial and contextual memories in rodents. While the role of the hippocampus on acquisition and retrieval of new memory (i.e., recent memory) is well established, its contribution to retrieval of old memory (i.e., remote memory) has remained a matter of debate. Here, we investigated a possible role of DG granule cells in retrieval of remote memory by using a novel immediate-early gene-based labeling system in mice, which enables to independently label cell ensembles activated during two memory retrieval tests with two different fluorescent proteins. Mice were trained in a contextual fear-conditioning paradigm, and analyzed for overlapping of the neuronal ensembles that were activated during the recall of recent memory and that of remote memory. We found that a small but significant population of DG neurons were reactivated during the retrieval of remote memory. We next optogenetically activated the Arc-positive DG neurons that were activated during remote memory recall. This manipulation caused induction of fear responses in an unconditioned context. Consistently, optogenetic suppression of the Arc-positive DG neurons significantly reduced fear responses in the conditioned context. These findings suggest that a subpopulation of hippocampal DG neurons contributes to memory recall processes even a long time after the acquisition.
| | 2020/9/10 9:20～9:40 Zoom B
SY1-02
文脈恐怖条件付け学習における記憶痕跡細胞の特異的活動
Specific activities of engram cells during contextual fear conditioning
*松尾 直毅1
1. 九州大学
*Naoki Matsuo1
1. Kyushu University
It is a fundamental question how memories are represented in the brain. A prevailing hypothesis suggests that memory is encoded by a cooperative activity of specific subset group of neurons. However, identifying these neurons supporting a given memory is challenging because these neuronal ensembles are likely sparsely distributed within the brain. To circumvent this difficulty, we have previously developed a transgenic system in mice that allows us to manipulate neurons activated during a relevant behavior. Activities of the tagged ensembles of neurons during contextual fear learning using this system have been shown to be sufficient and necessary for the contextual fear memory expression, demonstrating a direct evidence that individual memories reside in the activities of specific spatially distributed neuronal population within neuronal networks, or engram cells. However, the specific function of engram cells is not clear. In order to reveal the properties of engram cells, we have recently developed a transgenic system which allows us to monitor the calcium activities of engram cells during a given behavior. By using the combination of the transgenic system with an in vivo calcium imaging system, we recorded the activities of engram cells during contextual fear conditioning in mice. The analysis will provide a distinct role of engram cells in memory formation, retrieval and maintenance.
| | 2020/9/10 9:40～10:00 Zoom B
SY1-03
恐怖記憶再固定化・消去を制御する記憶痕跡細胞の同定と機能解析
Identification and characterization of reconsolidation/extinction engram
*石川 理絵1、喜田 聡1
1. 東京大学大学院
*Rie Ishikawa1, Satoshi Kida1
1. Graduate School of Agriculture and Life Sciences, The University of Tokyo
Brief fear memory retrieval triggers fear responses followed by memory reconsolidation, whereas long-time or repeated retrieval extinguishes fear memory. Memory circuits contributing to fear and extinction have been identified, respectively. However, discrimination and interaction of fear and extinction neurons have not well examined. We have identified and characterized “fear” and “extinction” neuron in the hippocampus, amygdala and mPFC using contextual fear conditioning and inhibitory avoidance tasks; c-fos positive neurons are increased in the mPFC, hippocampus and amygdala when fear memory is reconsolidated, while these neurons are increased in the mPFC and amygdala, but not hippocampus, when the memory is extinguished. To compare molecular signatures of reconsolidation and extinction, we measured phosphorylation of cAMP-responsive element-binding protein (pCREB) and extracellular signal-regulated kinase (pERK) following the retrieval of inhibitory avoidance memory. We found that neuronal population of these regions showed distinct molecular signatures in reconsolidation and extinction memory phases. Furthermore, we identified and compared fear and extinction neurons in these regions using Arc/Homer1a (H1a) catFISH. We found that amygdala showed distinct populations of reconsolidation and extinction neurons, respectively, suggesting that reconsolidation and extinction are regulated by distinct neuronal populations in the amygdala. More interestingly, mPFC showed only single neuronal population that is activated when memory is reconsolidated and extinguished, suggesting that reconsolidation and extinction are regulated by single neuronal population in mPFC. Now, we are trying to characterize reconsolidation and extinction engram neurons using optogenetics.
| | 2020/9/10 10:00～10:20 Zoom B
SY1-04
記憶痕跡セル･アンサンブルが織りなすエピソード記憶の脳内表現様式
Orchestrated ensemble activities of engram cells constitute an episodic memory
*大川 宜昭1
1. 獨協医科大学 先端医科学統合研究施設
*Noriaki Ohkawa1
1. Comprehensive Research Facilities for Advanced Medical Science, Dokkyo Medical University
The brain stores memories through a set of neurons, termed engram cells. It is unclear how engram cells are organized to constitute a corresponding memory trace. To extract the characteristics of population activity of engram cells, we established a unique imaging system by which engram cells were identified with a fluorescent protein, KikGR, and then the Ca2+ signals corresponding to the activity of engram cells and non-engram cells can be tracked during experience of a novel episodic event, exposure to novel context for 6 min. From correlation matrix analysis, it was indicated that population activity of engram cells exhibited highly repetitive activity during the novel episodic event. To address component of one memory, next, we proposed to deconstruct population activity into sub-ensemble groups. Non-negative matrix factorization (NMF) decomposes population activity into a time series of coactivated neuronal ensembles. Each sub-ensemble was composed of the different set of cells to make their synchronous activity, even among the group of engram cells associated with a single event. In addition, around 40% of the engram sub-ensembles formed during the novel experience were reactivated during sleep sessions and were preferentially reactivated during the retrieval session. By contrast, most non-engram ensembles that were activated during the novel episodic event were not reactivated in the later sessions. These results demonstrate that engram cells form several sub-ensembles defined by synchronous activities which survive through post-learning sleep sessions to contribute to the consolidation process. The present study sheds light on the relationship between ensemble activities and coding principles in learning and memory.
| | 2020/9/10 10:20～10:40 Zoom B
SY1-05
Identification of memory engram cells for understaing other's situation
北村 貴司
University of Texas Southwestern Medical Center
*Takashi Kitamura1
1. University of Texas Southwestern Medical Center
Individuals can learn about harmful stimuli and environments by observing other conspecifics in aversive situations. Observational fear (OF) is a mouse model of social fear learning in which a naïve observer witnesses an unfamiliar demonstrator receive foot-shocks in a modified contextual fear apparatus. Although the observer is not shocked, it freezes in response to demonstrator foot-shock and learns to fear the context. We define this as innate OF because the observer has neither shock experience nor is familiar with the demonstrator. However, in other cases in nature, both prior similar experience and familiarity with the demonstrator facilitates for observers to exhibit OF. We define this as experience-dependent OF. While the neural mechanisms of innate OF primarily depend upon the anterior cingulate cortex (ACC) and basolateral amygdala (BLA), the neural mechanisms of experience-dependent OF are unexplored. Here, we developed a mouse model of experience-dependent OF and then investigated the underlying neural mechanisms. Surprisingly, a chemical lesion in ACC failed to block experience-dependent OF, while the same lesion results in impairment of innate OF, indicating ACC has a specific role in innate OF but in not experience-dependent OF. Chemogenetic inhibition of excitatory neurons in dorsal hippocampus during own shock experience blocks experience-dependent OF. In ventral hippocampus, chemogenetic inhibition of excitatory neurons that project to the BLA during OF testing blocks experience-dependent OF. Currently, we hypothesize that dorsal hippocampus generates a fear memory engram in the BLA during own shock experience and ventral hippocampus reactivates the fear memory engram to express experience-dependent OF.
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