シンポジウム（Symposium）

Symposium Information Processing in Offline Brain シンポジウムオフライン状態の神経機構

7月25日（木）14:40～15:00　第5会場（朱鷺メッセ　3F　302） 1S05a-1 Sleep phenotype of cortical layer 5 silenced mouse Tomoko Yamagata（山形朋子）¹，Lukas B Krone（Krone B Lukas）^1,2，Anna Hoerder-Suabedissen（Hoerder-Suabedissen Anna）²，Zoltán Molnár（Molnár Zoltán）²，Vladyslav V Vyazovskiy（Vyazovskiy V Vladyslav）^1,2 ¹SCNi, NDCN, Univ Oxford, Oxford, UK ²DPAG, Univ Oxford, Oxford, UK Cortical layer 5 pyramidal neurons have been suggested to be a key component for the generation and the propagation of slow oscillation during sleep (Sanchez-Vives and McCormick, 2000; Chauvette et al, 2010; Beltramo et al, 2013). However, the consequences of selective silencing of these neurons for global sleep-wake architecture, sleep homeostasis or spontaneous cortical activity during sleep has not been studied. A conditional-knockout mouse Rbp4-Cre::Snap25fl/fl lacks the ability to release synaptic vesicles in a regulated fashion from around postnatal day 0 and ~15-30% of layer 5 pyramidal neurons are functionally silenced (Hoerder-Suabedissen et al, 2018). In this study, we investigated the sleep-wake pattern and cortical activity of the 'L5 silenced' mouse. Primarily, L5 silenced mice (Rbp4-Cre::Snap25fl/fl, cKO, n=6) showed an altered sleep-wake pattern as compared to Cre-negative control animals (Snap25fl/fl, Ctrl, n=6). Wake time increased during 24-hour recordings (Ctrl: 10.3 hrs, cKO: 13.2 hrs, p=0.037), resulting from extended wakefulness in the dark but not in the light period (Dark period, Ctrl: 7.1 hrs, cKO: 9.9 hrs, p<0.0001; Light period, Ctrl: 3.1 hrs, cKO: 3.3 hrs, p=0.6, student's t-test). We further investigated recovery sleep after 6-hour sleep deprivation. In control mice, EEG slow wave activity during NREM sleep (EEG-SWA, 0.5-4Hz) increased two-fold during recovery sleep compared to baseline sleep, and sleep time remarkably increased in the subsequent dark period. However, L5 silenced mice presented attenuated rebound of EEG-SWA and a modest increase in sleep time in the subsequent dark period. Our results suggest that the functional silencing of a subset of L5 pyramidal neurons changes spontaneous sleep-wake patterns and sleep homeostasis. Attenuation of sleep slow waves in L5 silenced mice was presented in recovery sleep after prolonged wakefulness, indicating that layer 5 is critical to SWA rebound in response to sleep deprivation. Hoerder-Suabedissen A et al. Cell-Specific Loss of SNAP25 from Cortical Projection Neurons Allows Normal Development but Causes Subsequent Neurodegeneration. Cereb Cortex, 2018. https://doi.org/10.1093/cercor/bhy127		7月25日（木）15:00～15:20　第5会場（朱鷺メッセ　3F　302） 1S05a-2 ショウジョウバエにおける睡眠中の概日時計と恒常性のスパイク発火パターンによる制御機構 Masashi Tabuchi（田渕理史）¹，Joseph D Monaco（Monaco D Joseph）²，Kechen Zhang（Zhang Kechen）²，Mark N Wu（Wu N Mark）¹ ¹Dept Neurology, Johns Hopkins Medicine, Baltimore, USA ²Dept Biomed Eng, Johns Hopkins Medicine, Baltimore, USA Sleep is regulated by two processes: circadian rhythm and homeostasis. Understanding the regulatory mechanisms of these processes is a prerequisite for defining a molecular pathway linking the circadian clock/homeostasis to temporal-specific neural coding in specific neural circuits to regulate sleep quality and sleep drive. In terms of circadian regulation of sleep, we recently demonstrated that spiking patterns of Drosophila clock neurons are used as temporal codes to control sleep quality (Tabuchi et al., Cell 2018). We first found that the clock neuron network in Drosophila exhibits distinct temporal patterns of spiking during the day vs. the night. Optogenetic manipulation revealed that these temporal codes drive alterations in clock-regulated sleep. Using a large-scale genetic screen, we delineated the molecular processes by which the circadian clock generates distinct temporal codes. Moreover, we addressed how specific spiking pattern in a circadian circuit alters sleep/wake behavior, by characterizing effects on a downstream arousal circuit. We showed that specific spiking patterns in the upstream clock neurons induce a dramatic increase in the firing rate of the downstream arousal circuit. Remarkably, this phenomenon involves synaptic plasticity that depends solely on the spiking pattern. These data demonstrate a form of synaptic plasticity being directly induced by changes in the pattern, but not the rate or timing, of neuronal firing. In terms of sleep homeostatic drive, we recently identified a subset of ellipsoid body neurons whose activation generates sleep drive in Drosophila (Liu et al., Cell 2016). We also found that these neurons are highly sensitive to sleep loss, switching from spiking to burst-firing modes with NMDA receptor expression specific manner. Moreover, we now reveal that these neurons exhibit burst-firing modes-dependent morphological changes to increase the functional connectivity with a downstream circuit during sleep deprivation, acting as sleep deprivation-dependent relay switch mechanism for transmission of homeostatic sleep drive in Drosophila.

7月25日（木）15:20～15:40　第5会場（朱鷺メッセ　3F　302） 1S05a-3 哺乳類の能動的低代謝のモデルとしてのマウス日内休眠を Genshiro A. Sunagawa（砂川玄志郎）理化学研究所生命機能科学研究センター網膜再生医療研究開発プロジェクト Some mammals enter a hypometabolic state either daily torpor (minutes to hours in length) or hibernation (days to weeks), when reducing metabolism would benefit survival. The metabolic rate is reduced to 1~30% of normal rates and animals sacrifice their vital biological functions such as consciousness and mobility to save metabolism, which makes them look offline. The mechanisms for such hypothermia-resistance and hypometabolism-resistance is not understood. Hibernators demonstrate deep torpor by reducing both the sensitivity (H) and the theoretical set-point temperature (TR) of the thermogenesis system, resulting in extreme hypothermia close to ambient temperature. However, these properties during daily torpor in mice remain poorly understood due to the very short steady state of the hypometabolism and the large variation among species and individuals. To overcome these difficulties in observing and evaluating daily torpor, we developed a torpor-detection algorithm based on Bayesian estimation of the basal metabolism of individual mice. Applying this robust method, we evaluated minimal body temperature (TB) and oxygen consumption rate (VO2) of fasting-induced torpor in C57BL/6J mice (B6J) under various ambient temperatures (TAs) and found that H decreased 91.5% during daily torpor while TR only decreased 3.79 °C in mice (Sunagawa GA and Takahashi M, Sci Rep, 2016). Furthermore, we found that C57BL/6N (B6N) have distinct torpor phenotypes from B6J (GA Sunagawa, 2018, BioRxiv 374975). When the TA is 20 °C, the 89% highest posterior density interval (HPDI) of TB (°C) were [31.4, 34.2] and [27.3, 30.5], and 89% HPDI of VO2 (ml/g/h) were [1.75, 2.57] and [1.01, 1.45], respectively for B6N and B6J. These data are showing that B6N has higher metabolism during torpor than B6J. Interestingly, in both B6J and B6N mice strains, H is decreased as hibernators, but TR remains relatively unchanged during daily torpor. To investigate whether the stable TR during torpor is a common feature in mice, we have evaluated various inbred strains and found that in some strains TR may be reduced than B6J or B6N mice. Because TR is controlled centrally in mammals, suggested mechanism of neural regulation of body temperature during active hypometabolism (hibernation and daily torpor) is reviewed, and our hypothesis of central regulation of active hypometabolism will be shared.		7月25日（木）15:40～16:00　第5会場（朱鷺メッセ　3F　302） 1S05a-4 The role of sleep hippocampal ripples for memory consolidation Gabrielle Girardeau（Girardeau Gabrielle） Institut du Fer-a-Moulin, Inserm, Sorbonne Universite The hippocampus and the amygdala are two structures required for emotional memory. The hippocampus, through place cells, is believed to encode the spatial or contextual part of the memory. During slow-wave sleep, the activity of place cells is replayed in the same order as during the preceding learning epoch. These reactivations specifically occur during local field potential (LFP) short oscillatory events associated with highly synchronous neuronal activity called ripples. Our early work shows that the specific suppression of ripples during sleep impairs performance on a spatial task, underlying their crucial role in memory consolidation. On the other hand, the amygdala processes the emotional valence of an event. How do the amygdala and the hippocampus interact to consolidate an emotional event? Are hippocampal ripples involved in the association between a specific context and an aversive event? Using large scale simultaneous neuronal ensemble recordings in the hippocampus and amygdala, we found ripple-related coordinated reactivations between the two structures during sleep following training on an aversive spatial task. Hippocampal ripples during sleep thus emerge as a crucial time windows for intra-hippocampus and cross-structure reactivations sustaining the consolidation of spatial and emotional memories.

7月25日（木）16:00～16:20　第5会場（朱鷺メッセ　3F　302） 1S05a-5 Cuttlefish behavior at cellular resolution reveals spontaneous neural activity Sam Reiter（Reiter Sam） Max Planck Institute for Brain Research Spontaneous neural activity is pervasive in the vertebrate brain, underlying functions from neural development to memory formation. Within the hippocampus, spontaneous activity during sleep and quiet wakefulness takes the form of sequences of neuronal activation that `replay' those seen during active behavior. Among other theories, this has been hypothesized to represent memory access supporting temporal credit assignment (ref. 1). Coleoid cephalopods (cuttlefish, octopus and squid) offer a unique opportunity to test for the presence and structure of spontaneous activity in animals who evolved large brains and complex behaviors independently from the vertebrate lineage. In order to camouflage with their surroundings, these animals evolved high resolution skin display systems where aspects of brain state are played out through direct neural control over the expansion and contraction of hundreds of thousands of pigment-filled cells known as chromatophores. Extending on our recent work in cuttlefish (ref. 2), We built an array of cameras and combined deep neural networks with nonlinear alignment techniques to identify and track >100,000 individual chromatophores simultaneously in freely behaving cuttlefish. Surprisingly, while camouflaging to a static background, a cuttlefish's chromatophores display large amounts of spontaneous activity. We used the statistical structure of this spontaneous activity to infer putative elements of a hierarchical motor control strategy. This starts with motor neurons directly coordinating the activity of small groups of chromatophores and proceeds to larger-scale pattern elements. While sleeping, cuttlefish have been reported to undergo rapid and dramatic skin pattern changes (ref. 3). We will explore this phenomenon in the context of experience replay in vertebrates, and discuss the possible implications for sleep and neural computation. References: 1) Mattar MG. & Daw ND., Nature Neuroscience, 2018 2) Reiter S. et al., Nature, 2018 3) Iglesias T. et al, Journal of Experimental Biology 2018		7月25日（木）16:20～16:40　第5会場（朱鷺メッセ　3F　302） 1S05a-6 カルシウム依存的な過分極経路の睡眠恒常性における役割の理解 Shoi Shi（史蕭逸）^1,2,3，Hiroki R. Ueda（上田泰己）^1,2,3 ¹東京大学大学院医学系研究科機能生物学専攻システムズ薬理学教室 ²理化学研究所　生命機能科学研究センター ³東京大学　ニューロインテリジェンス国際研究機構 Although we are beginning to understand the neuronal and biochemical nature of sleep regulation, questions remain about how sleep duration is controlled and how sleep is homeostatically regulated. Recent genetic studies in mammals revealed several non-secretory proteins that determine sleep duration, raising a possibility that sleep duration might be regulated by an intracellular molecular mechanism. To understand the molecular basis of sleep, we combined mathematical analysis and comprehensive KO study. We constructed two simple computational models of an averaged neuron (the AN model: Averaged-Neuron model, the SAN model: Simplified-Averaged-Neuron model), which recapitulate the electrophysiological characteristics of the slow-wave sleep. Comprehensive bifurcation analysis of an ensemble of more than 1,000 models predicted that a Ca2+-dependent/independent hyperpolarization pathways may play a role in slow-wave sleep and hence in sleep-duration regulation. To experimentally validate the prediction, we performed a comprehensive KO study and succeeded in identifying the genes (Kcnn2, Kcnn3, Kcnk9, Atp2b3, Cacna1g, Cacna1h, Camk2a, Camk2b, and Nr3a) included in Ca2+-dependent/independent hyperpolarization pathways playing a role in sleep-duration regulation. Based on these results, we hypothesize that the Ca2+-dependent/independent hyperpolarization pathways cooperatively regulate sleep duration in mammals. References: Sunagawa et al., 2016, Tatsuki et al., 2016, Yoshida et al., 2018