シンポジウム
34 脳情報表現の時間的変容への光学的アプローチ: 行動からシナプスまで
34 Optical approaches to temporal transformations of brain informationrepresentations: from behavior to synapses.
座長：宮本 大祐（富山大学研究推進機構アイドリング脳科学研究センター）・後藤 明弘（京都大学大学院医学研究科） |
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| 2022年7月1日 16:10～16:34 沖縄コンベンションセンター 会議場B5～7 第4会場
2S04e-01
記憶固定化におけるシナプス可塑性の時間枠を検出する新規光遺伝学ツール
A new optogenetic tool for identifying the time window of synaptic plasticity during memory consolidation.
*後藤 明弘(1)
1. 京都大学大学院 医学研究科 システム神経薬理
*Akihiro Goto(1)
1. Department of Pharmacology, Kyoto University Graduate School of Medicine
Keyword: Synaptic plasticity, Memory consolidation, optogenetic, CALI
The memory is initially formed in the hippocampus but subsequently transferred to the rest of brain, in a process called memory consolidation. Synaptic plasticity plays an important role in the process of memory consolidation. However, it has not been fully elucidated when and where such plasticity occurs. In order to detect the time frame in which synaptic plasticity occurs, we developed a new photogenetic method to eliminate LTP by light (Goto et al., 2021, Science 374, 857-863 ).
Cofilin, an actin-related molecule, enters the spine with LTP and plays an important role in postsynaptic spine enlargement (sLTP, structural LTP). Therefore, we fused SuperNova, a photosensitizing protein that induces CALI with high efficiency, with cofilin (Cofilin-SuperNova) and expressed it in spines. Since this technique can eliminate only LTP induced within 20 minutes, the time at which LTP was induced can be analyzed by light illumination.
When Cofilin-SuperNova was expressed in the hippocampus by adeno-associated virus and exposed to light immediately after learning or during the subsequent sleep period in the home cage, memory was erased in each case. In the anterior cingulate cortex (ACC), light exposure during sleep on the day after learning erased memory. These results indicate that LTP occurs in the hippocampus immediately after learning and during sleep, and further LTP occurs in the anterior cingulate cortex during sleep on the following day.
Furthermore, by observing neural activity in combination with calcium imaging using miniature microscopy, we revealed the process by which hippocampal cell activity acquires synchronous firing properties through synaptic plasticity.
In summarry, by using a new opotogenetic tool, we reveal the spatiotemporal information of synaptic plasticity and the associated cellular activity that occurs in the early stages of memory consolidation. | | 2022年7月1日 16:34～16:58 沖縄コンベンションセンター 会議場B5～7 第4会場
2S04e-02
Hormonal regulation of limbic-hypothtlamic circuits for social behaviors in female mice
*Takashi Yamaguchi(1)
1. New York University
Keyword: social behaviors, limbic-hypothalamic circuits, estrogen, optical recording
Fluctuations in circulating hormones during pregnancy and postpartum periods are believed to influence emotional states in females. Indeed, hormonal changes can have negative health consequences, such as vulnerability to social stress during these periods. Lactating animals across species show aggressive behaviors to protect infants from threats. It is likely that lactating females perceive confrontations with intruders as more threatening, and therefore adopt defensive behaviors to protect their offspring. Thus, the brain circuit involved in maternal aggression is the optimal target to assess how circulating hormones change neural responses to social targets and shape maternal brain that drives emotional behaviors to social stressors. The estrogen surge during pregnancy is believed to stimulate maternal aggression. Indeed, estrogen receptor alpha expressing (Esr1+) cells in the ventrolateral hypothalamus ventrolateral part (VMHvl), serve as a regulatory hub for aggressive behaviors in both males and females (Lee et al., 2014, Hashikawa et al., 2017). However, the circuit level understanding how the VMHvl coordinates aggressive behaviors in females remains unknown. I recently established circuit-specific recording and manipulation approaches by combining virus-mediated gene transfer with transgenic tools to understand the circuit-level mechanism of social behaviors (Yamaguchi et al., 2020). Using these approaches, I identified Esr1-expressing cells in the posterior amygdala (PA) as a main source of excitatory inputs into the VMHvl and key driving force of aggressive behaviors in both males and females. Furthermore, longitudinal photometry recording demonstrated Esr1+ cells in the PA displayed higher responses to social targets in lactating dams, compared with virgins. Combing a hormone priming regimen and optical recording, I found estrogen enhances the activity of Esr1+ cells in the PA. These findings demonstrated how circulating hormones change neural responses to drive aggressive behaviors corresponding to a reproductive-state. | | 2022年7月1日 16:58～17:22 沖縄コンベンションセンター 会議場B5～7 第4会場
2S04e-03
Reading m6A RNA modification signals in neurons and at the synapses
*Dan Ohtan Wang(1)
1. RIKEN-BDR, Kobe, Japan
Keyword: N6-methyl-adenosine, synapse, spine, reader
N6-Methyladenosine (m6A) RNA modification is a highly prevalent RNA modification expressed with abundance in the mammalian brain. In recent years, m6A signal has been shown to be required for fundamental brain functions such as development, regeneration, learning and memory, circadian rhythm, and more. But how the signals are transduced into neuronal and synaptic functions remains poorly understood. Previously, we have cataloged synaptically localized m6A-modified transcripts in synaptosomes, which included thousands of modified transcripts involved in neurodevelopmental and neuropsychiatric pathways. Now to understand how in dendrites and axons of neurons is the m6A signal decoded, we focused on two cytoplasmic m6A reader YTH family proteins: YTHDF1 and YTHDF3, and generated transgenic mice models with specific deletion of YTHDF1 or YTHDF3 in mature excitatory neurons. Using a high throughput fluorescence imaging methods, we performed morphometric analysis on thousands of spines in each animal in cortex, hippocampus, and amygdala. We observed massive alterations. Interestingly the alterations differed in brain regions and in branch-types, supporting functional relevance of m6A signals to local spine development and furthermore the circuit connectivity through excitatory synaptic transmission. | | 2022年7月1日 17:22～17:46 沖縄コンベンションセンター 会議場B5～7 第4会場
2S04e-04
Dynamic synaptic engram
*Kaang Bong-Kiun(1)
*Bong-Kiun Kaang(1)
1. School of Biological Sciences, Seoul National University, Korea
Keyword: engram, synaptic plasticity, dendritic spine, dual eGRASP
With the advent of diverse molecular, cellular and behavioral tools, it became possible to better understand how memory is acquired and stored precisely in molecular and cellular terms. Combined with the concept of engram which refers the physical structure of memory in the brain, the field of learning and memory has drawn much attention in neuroscience. However, it is still not clear how much synapses between engram cells in different brain regions contribute to the memory formation. Therefore, we have asked how memory formation strengthens synapses between engram cells. In this talk, I will present our recent structural approaches to reveal enhanced structural connectivity between engram cells in the hippocampus and amygdala during fear memory formation. I will also discuss the dynamic nature of synaptic engram during the memory formation. | | 2022年7月1日 17:46～18:10 沖縄コンベンションセンター 会議場B5～7 第4会場
2S04e-05
アイドリング脳の活動と機能への光学的アプローチ
Optical approaches to activities and functions of the idling brain
*井ノ口 馨(1)
1. 富山大学学術研究部医学系
*Kaoru Inokuchi(1)
1. Grad Sch Med, University of Toyama
Keyword: IDLING BRAIN, MEMORY ENGRAM, TRANSITIVE INFERENCE, SLEEP
Neurons in the brain are active even when animals sleep or rest, denoted here by “idling brain state”. Flexible reorganization of previously acquired knowledge underlies higher-order brain functions, such as inference, assimilation, decision making, schema, and creative thinking. Inferential reasoning is a prominent property of higher-order cognition and relies on the systematic organisation of existing knowledge. It has been proposed that sleep facilitates inference, insight and innovative problem-solving. However, it remains unclear how and when the subconscious, but not conscious, brain can create novel ideas. Here, we show that cortical offline, but not online, activity is essential for inference evolution and that activity in rapid-eye movement (REM) sleep-specific brain circuitry is sufficient to inspire inference from inadequate knowledge. In a transitive inference paradigm, mice learned the relationship between five different contexts and could infer novel information that had never been experienced. Mice gained the inference one day, but not shortly, after the complete training. Inhibiting the neuronal computations in the anterior cingulate cortex (ACC) during post-learning sleep, but not during wakefulness, disrupted the inference without affecting the original memories. Furthermore, after insufficient learning, artificial activation of medial entorhinal cortex-ACC dialogue during only REM sleep created inferential knowledge. Our results indicate that cortical offline, but not online, activity is essential for inference evolution and activity during REM sleep is sufficient to inspire inference from inadequate knowledge. Our findings highlight the power of the idling brain in cognitive flexibility. | | | |
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