Symposium
Brain-state dynamics underlying consciousness and cognition
シンポジウム
脳状態ダイナミクスと意識・認知機能 |
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| 7月27日（土）9:05～9:25 第5会場（朱鷺メッセ 3F 302）
3S05m-2
覚醒−睡眠のサイクルにおける海馬の記憶情報処理機構
Kenji Mizuseki（水関 健司）
大阪市立大学大学院医学研究科
A two-stage memory consolidation model states that, during waking theta states, the afferent activity between the neocortex and the hippocampus transiently modifies hippocampal synapses. Such modification involves the deposition of information as labile memory traces. During the subsequent non-theta states, the transfer of newly acquired hippocampal information to distributed circuits, including the neocortex, in support of memory consolidation, is thought to be mediated by the synchronous activity of neuronal populations in patterns designated as sharp-wave ripples (SPW-Rs). SPW-Rs contain fragments of time-compressed neuronal sequences that are replayed from those experienced during waking hours (Buzsaki, 1989). Consistent with this hypothesis, waking theta and non-theta states distinctly control the flow of information in the hippocampal-entorhinal loop, and the perturbation of neuronal activity during SPW-Rs can lead to memory impairment. Both the waking theta states and the rapid eye movement sleep are characterized by prominent hippocampal theta oscillations. However, each of these brain states involves distinct temporal coordination and oscillatory coupling in the hippocampal-entorhinal circuit, which reflect the distinct balance of hippocampal and entorhinal input to the CA1 area.
The hippocampal formation comprises the dentate gyrus, hippocampus proper, and subiculum. The subiculum receives direct synaptic inputs from the hippocampal CA1 area and projects to various cortical and subcortical areas, thereby playing a crucial role in the organization of the hippocampal output. Several features distinguish the subiculum from the CA1 area, including its laminar structure, cellular composition, synaptic plasticity, behavioral role, neural oscillation, and spatial/non-spatial representation, suggesting that it exerts a unique function in processing information (Matsumoto et al., 2019). Despite the postulated importance of the subiculum, the nature of information distribution from the subiculum to downstream areas, especially in the context of brain-state-dependent information processing, remains largely unknown. To investigate this issue, we devised a method to optogenetically identify the projection targets of individual subicular neurons during large-scale extracellular recordings in freely behaving rats. We examined target-specific information processing in the subiculum across sleep/wake cycles. | | 7月27日（土）8:45～9:05 第5会場（朱鷺メッセ 3F 302）
3S05m-1
睡眠覚醒状態変化に関わる神経回路の機能的同定
Akihiro Yamanaka（山中 章弘）
名古屋大学環境医学研究所
Brain state change such as sleep and wakefulness is regulated by neurons, however, its regulatory mechanism is still unclear. Here we found that GABAergic neurons in the ventral tegmental area (VTA) have an important role in the regulation of sleep/wakefulness. Adeno-associated virus (AAV) vectors were injected into VTA of glutamic acid decarboxylase (GAD)-Cre mice in which GABAergic neurons are exclusively express Cre recombinase. To manipulate GABAergic neurons in the VTA, channelrhodopsin2 (ChR2), anion-channelrhodopsin2 (ACR2) or hM3Dq was expressed by AAV. Chemogenetical activation of these neurons significantly increased time in NREM sleep with increased delta activity in electroencephalogram (EEG). To reveal neural mechanism, slice patch clamp was performed. AAV was injected to VTA to express ChR2 in the GABAergic neurons in the VTA. Orexin neurons expressing fluorescent protein were identified and recorded. Then, GABAergic nerve terminals from VTA were stimulated by blue light. Blue light significantly inhibited activity of orexin neurons. On the other hand, optogenetical inhibition of these neurons using ACR2 immediately induced wakefulness. To evaluate physiological importance of this response, these neurons were inhibited during recovery sleep after sleep deprivation for 4 hr. Inhibition of GABAergic neurons induced wakefulness even in the very sleepy condition. These results suggest that activity of GABAergic neurons in the VTA is critical to change sleep/wakefulness state especially in the regulation of NREM sleep and wakefulness. | | 7月27日（土）9:25～9:55 第5会場（朱鷺メッセ 3F 302）
3S05m-3
Consciousness and Brain Complexity: an exploration across scales and models
Marcello Massimini（Massimini Marcello）
University of Milan
Theoretical neuroscience suggests that consciousness depends on the ability of neural elements to engage in complex activity patterns that are, at once, distributed within a system of interacting cortical areas (integrated) and differentiated in space and time (information-rich) (i.e. brain complexity). Based on this principle, we have been developing and testing a theory-driven empirical method to assess brain complexity based on a combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG). Overall, the assessment of brain complexity provides a reliable measuring scale along the unconsciousness/consciousness spectrum and allows a robust assessment of unresponsive individuals (such as locked-in, minimally conscious and vegetative state patients) whose level of consciousness cannot be assessed behaviorally.
Starting from the experimental evidence of a link between consciousness and complexity, we moved on to explore the mechanisms by which brain complexity collapses and recovers in the human brain. Specifically, we wanted to test the hypothesis that neuronal bistability: the intrinsic tendency of cortical neurons to fall into a silent OFF-period after an initial activation - may play an important role in impairing the brain's capacity to integrate information not only during NREM sleep but also in anesthesia and in brain-injured patients. We try to address this question at multiple scales (macro, meso and micro) of investigation, by recording brain responses to direct cortical stimulations using (1) TMS/EEG, (2) intracranial electrical stimulation/recordings in neurosurgical patients as well as in the animal model and (3) cortical slices. These measurements provide convergence evidence that bistability and neuronal OFF-periods may play an important role in preventing the build-up of brain complexity. Since bistability is, in principle, a reversible dynamics, this finding may point to novel strategies to promote recovery of consciousness after brain injury. | | 7月27日（土）9:55～10:15 第5会場（朱鷺メッセ 3F 302）
3S05m-4
睡眠・覚醒を通じた視床・皮質の神経活動ダイナミクス
Sakiko Honjoh（本城 咲季子）
筑波大 国際統合睡眠医科学研究機構
Sleep is a robust and tightly regulated biological process, in which our consciousness and cognitive ability reproducibly fluctuate. There are two types of sleep: non-rapid eye movement (NREM) sleep, which makes up ~80% of sleep and rapid eye movement (REM) sleep, which occurs in relatively short episodes. Usually we remain unconscious during deep NREM sleep, whereas we dream during REM sleep. Therefore, it will be of particular interest to compare neural activities across those different vigilance stages, i.e., wake (conscious and connected to the environment), NREM sleep (unconscious), and REM sleep (dreaming and disconnected from the environment).
The cortex is believed to be critical for arousal and cognitive function. The low-voltage fast frequency activity pattern in cortex, so called `activated EEG', is one of the most sensitive markers of consciousness. The thalamus is reciprocally connected to the cortex and plays an important role in sensory information processing, as shown by the fact that all sensory information, except for olfaction, is relayed through thalamus to cortex.
Here we focused on a neural subpopulation in the thalamus,""matrix cells"", which project to widespread cortical areas and whose function remained unknown. We found that matrix cell activity is highly correlated with activated EEG, with sustained high firing during wake and REM sleep and low firing during NREM sleep in freely behaving mice. Thalamic matrix cells increased firing before cortical activation in both transitions from NREM sleep to wake or REM sleep, suggesting its role in cortical activation. To investigate its causal role, we employed optogenetic stimulation and found that high frequency stimulation of matrix cells elicits cortical activation and behavioral arousal from NREM sleep. However, interestingly, the identical optogenetic stimulation failed to promote arousal from REM sleep showing the vigilance state-dependent thalamo-cortical interaction. To address the underlying neural mechanisms, we analyzed Granger Causality (GC) between the cortex and the thalamus. Our analyses revealed that GC from thalamus to cortex is the highest during wake and the lowest during REM sleep. The low causality from thalamus to cortex during sleep could be a potential mechanism for the vigilance state-dependent fluctuation of consciousness and cognition. | |
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