Oral
Learning, Memory and Plasticity-1
一般口演
学習・記憶・可塑性-2 |
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| 7月27日（土）15:20～15:35 第9会場（朱鷺メッセ 3F 306+307）
3O-09a2-1
ノルアドレナリン作動性ドパミンD1受容体活性化による海馬シナプス修飾
Katsunori Kobayashi（小林 克典），Hidenori Suzuki（鈴木 秀典）
日本医科大医薬理
The central catecholaminergic system has been implicated in the pathophysiology of psychiatric disorders and neuronal mechanism of their therapeutic treatments. We have previously shown that dopamine can induce robust potentiation at the hippocampal mossy fiber (MF)-CA3 excitatory synapse via activation of D1-like receptors. This dopamine-induced synaptic modulation is strongly enhanced by chronic antidepressant treatment and electroconvulsive treatment, suggesting potential importance in antidepressant action. However, the dopaminergic projection to the hippocampus has been reported to be sparse. It is unknown whether endogenous dopamine can sufficiently activate D1-like receptors at the MF synapse. In the present study, we characterized D1-like receptor-dependent modulation of MF synaptic transmission mediated by endogenous catecholamines using mouse hippocampal slices. Bath-applied methamphtetamine, a releaser of monoamines, induced slowly developing synaptic potentiation. While the methamphtetamine-induced synaptic potentiation was strongly enhanced by electroconvulsive treatment similarly to the dopamine-induced potentiation, it was largely suppressed by a serotonin 5-HT4 receptor antagonist, suggesting that serotonin is the major endogenous transmitter mediating the effect of methamaphetamine. In the 5-HT4 receptor knockout mice, methamphetamine caused small, but significant, synaptic potentiation. This 5-HT4-independent potentiation was blocked by a D1-like receptor antagonist, an inhibitor of the noradrenaline transporter and the noradrenergic neurotoxin DSP-4. Furthermore, the 5-HT4-independent potentiation was greatly enhanced by administration of dopa, a precursor of dopamine. These results suggest that endogenous catecholamines released from noradrenergic fibers can potentiate MF synaptic transmission via activation of D1-like receptors. | | 7月27日（土）15:35～15:50 第9会場（朱鷺メッセ 3F 306+307）
3O-09a2-2
文脈依存的恐怖記憶の記銘、想起及び消去時における海馬CA1細胞のカルシウムイメージング
Kyogo S Kobayashi（小林 S 暁吾）1，Ren Takakura（高蔵 蓮）2，Jun-nosuke Teramae（寺前 順之介）2，Naoki Matsuo（松尾 直毅）1
1大阪大院医分子行動神経科学
2京都大院情報先端数理科学
Animals acquire a fear memory upon encounter a dangerous situation, and they make full use of the memory upon re-encounter the same situation to survive. Contextual fear conditioning is a powerful behavioral paradigm to study the neural mechanism of learning and memory. In this paradigm, a mouse is placed in a neutral context, which is characterized by a variety of environmental cues, such as floor textures, lighting intensity, background noise, odors of the chamber. Several minutes later, electrical foot shock is administered and the mouse is removed from the context. When the mouse is returned to the same context, it exhibits freezing behavior as a result of fear memory retrieval. Subsequent repeated re-exposure to the context without foot shocks eventually results in an attenuation of freezing behavior. Thus, contextual fear conditioning is useful for the analysis of memory encoding, retrieval, and extinction. Although a number of studies have demonstrated that the hippocampus is indispensable for contextual learning, a number of mysteries still remain unexplained: (1) what kind of cell would become a memory engram cell, (2) how hippocampal neurons encode contextual information, and (3) how hippocampal context representations are affected by fear memory extinction. To tackle these issues, we monitored calcium dynamics of 2,359 hippocampal CA1 pyramidal cells from 11 mice using a head-mounted microendoscope at single-cell resolution during contextual fear learning. We thereby analyzed the activity of each neuron at different time points (before, during, or after foot shocks), different contexts (fear-conditioned context, distinct context, or home cage), and different behavioral states (freezing or non-freezing). In this meeting, we will present our recent findings about the neuronal activity patterns observed in the CA1 and discuss the association between the neural activity and behavior. | | 7月27日（土）15:50～16:05 第9会場（朱鷺メッセ 3F 306+307）
3O-09a2-3
慢性的な貧栄養ストレスによる報酬刺激物質への嗜好性の変化
Toshiharu Ichinose（市之瀬 敏晴）1,2,3，Mai Kanno（菅野 舞）2，Shu Kondo（近藤 周）4，Shun Hiramatsu（平松 駿）2，Ayako Abe（阿部 綾子）2，Sena Hatori（羽鳥 聖七）3，Riho Kobayashi（小林 里帆）3，Kazuhiko Kume（粂 和彦）3，Hiromu Tanimoto（谷本 拓）2
1東北大 学際科学フロンティア研究所
2東北大院生命科学
3名古屋市立大 薬学研究科
4国立遺伝学研究所
Sub-optimal environment is a risk factor for development of substance abuse. For example, human studies have been repeatedly reporting a strong correlation between stressful life events and drug abuse or obesity (Ruisoto et al., 2018, Physiology and Behavior). However, current understanding of the physiological mechanism is limited due to the lack of effective genetic tools. Therefore using a genetically tractable model system, Drosophila melanogaster, we aimed to establish an experimental model to understand how the chronic stress modulates preference for rewarding substances. We found that chronic malnutrition remarkably enhances preference for multiple rewarding stimuli, e.g. sugar, alcohol and methamphetamine. We provide evidence that long-lasting malnutrition and acute starvation cause fundamentally different behavioral changes. Dopamine has been known to play a key role in mediating reward information in Drosophila (Liu et al., 2012, Nature). Blockade of dopamine release and mutation in one of the dopamine receptors erased the behavioral alteration, revealing a critical role of the dopamine system. Moreover, we found that the chronic malnutrition changes dopamine synthesis and the receptor composition. These results imply that experience-dependent sensitization of dopamine synapses changes reward preference. Therefore, our study provides a neuronal insight how the brain adapts to its environments and changes the behavior. | | 7月27日（土）16:05～16:20 第9会場（朱鷺メッセ 3F 306+307）
3O-09a2-4
記憶を行動に変換する回路と、記憶に基づいてドーパミン細胞の活動を制御する回路の共通項
Yoshinori Aso（麻生 能功）
Janelia Research Campus, Virginia, USA
Animals discriminate stimuli and learn their predictive value based on temporal correlation with reinforcements (reward or punishment). Synaptic modulation by dopamine is essential for such associative learning and adaptive behaviors in all animal phyla. Induction of synaptic plasticity by dopaminergic neurons (DANs; i.e. neurons that synthesize and release dopamine), in turn, affects how DANs respond to reinforcement and learned stimuli. In that way, learning adjusts how and what animals learn thereafter. Thus understanding molecular mechanisms that regulate how DANs modulate synaptic connection and intricate circuit mechanism that adaptively regulate activity of DANs, and their interplays are essential for comprehensive understanding of dopaminergic system.
The Drosophila mushroom body (MB), a key center for associative learning in insect brains, provides an excellent system to study the mechanisms of dopamine-mediated plasticity and learning. In the MB, sparse activity patterns in the 2,000 Kenyon cells represent the identity of sensory stimuli. Along the parallel axonal fibers of Kenyon cells, DANs and MB output neurons form 16 matched compartmental units. These anatomically defined units are also units of associative learning and heterosynaptic plasticity. Reward and punishment activate distinct subsets of 20 types of DANs. Individual DANs write and update memories independently in each unit with cell-type-specific rules by modulating synaptic connection between Kenyon cells and MB output neurons. In response to the learned odor, the activity of 21 types of MB output neurons (MBONs), having been adjusted by plasticity, act together as a population code to represent the predictive value of sensory cues.
Our prior work generated a collection of ~100 split-GAL4 driver lines that allow expression of transgenes in any of MB's 60 cell types with single cell type specificity. Now we have generated additional ~400 driver lines for the cell types that have significant overlap with DANs and MBONs, and utilized them to analyze their behavioral and physiological functions. We were particularly interested in the circuit that integrate signals from multiple MBONs for memory-based action selection and adaptively encoding reinforcement signal by feeding signals back to DANs. We have identified one cell type essential for both processes, and will discuss about its implications.
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