researchmap

researchmap

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Zoological Society of Japan  

DOI： 10.2108/zs230123

Web of Science

Scopus

PubMed

researchmap

Language：English   Publisher：Journal of Biological Rhythms  

Animals frequently experience temperature fluctuations in their natural life cycle, including periods of low temperatures below their activity range. For example, poikilothermic animals are known to enter a hibernation-like state called brumation during transient cooling. However, the knowledge regarding the physiological responses of brumation is limited. Specifically, the impact of exposure to low-temperature conditions outside the range of temperature compensation on the subsequent circadian behavioral rhythms remains unclear. In this study, we investigated the effects of transient cooling on the behavioral circadian rhythm in the non-avian reptile, the bearded dragon (Pogona vitticeps). Under constant light (LL) conditions at 30 °C, the animals exhibited a free-running rhythm, and exposure to low temperatures (4 °C) caused a complete cessation of locomotion. Furthermore, we revealed that the behavioral rhythm after rewarming is determined not by the circadian phase at the onset or the duration of cooling, but by the timing of cooling cessation.

DOI： 10.1177/07487304241273190

Web of Science

Scopus

PubMed

Language：English   Publisher：The journal of physiological sciences : JPS  

An increase in ambient temperature leads to an increase in sleep. However, the mechanisms behind this phenomenon remain unknown. This study aimed to investigate the role of microglia in the increase of sleep caused by high ambient temperature. We confirmed that at 35 °C, slow-wave sleep was significantly increased relative to those observed at 25 °C. Notably, this effect was abolished upon treatment with PLX3397, a CSF1R inhibitor that can deplete microglia, while sleep amount at 25 °C was unaffected. These observations suggest that microglia play a pivotal role in modulating the homeostatic regulation of sleep in response to the fluctuations in ambient temperature.

DOI： 10.1186/s12576-024-00929-0

Web of Science

Scopus

PubMed

Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.jphs.2024.03.003

researchmap

DOI： 10.1101/2024.03.19.585680

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Although diurnal animals displaying monophasic sleep patterns exhibit periodic cycles of alternating slow-wave sleep (SWS) and rapid eye movement sleep (REMS), the regulatory mechanisms underlying these regular sleep cycles remain unclear. Here, we report that in the Australian dragon Pogona vitticeps exposed to constant darkness (DD), sleep behavior and sleep-related neuronal activity emerged over a 24-h cycle. However, the regularity of the REMS/SWS alternation was disrupted under these conditions. Notably, when the lizards were then exposed to 12 h of light after DD, the regularity of the sleep stages was restored. These results suggest that sleep-related neuronal activity in lizards is regulated by circadian rhythms and that the regularity of REMS and SWS cycling is influenced by daytime light exposure.

DOI： 10.1093/pnasnexus/pgad481

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Public Library of Science (PLoS)  

Memory is a fundamental brain function that can be affected by a variety of external factors including environmental pollutants. One of these pollutants is methyl vinyl ketone (MVK), a hazardous substance found in cigarettes, industrial wastes, and car exhaust. Humans can be exposed to MVK under many circumstances; however, it is unclear whether MVK affects higher-order brain functions such as memory. Here, we examined the memory performances of mice receiving systemic MVK administration. We found that 1 mg/kg of MVK impaired spatial memory. We also showed that 1 mg/kg MVK activated glial cells and altered glial functions in several subregions of the hippocampus, a brain region involved in learning and memory. These results suggest that MVK induces memory deficits and activates glial cells in hippocampal subregions.

DOI： 10.1371/journal.pone.0289714

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Microglia, as macrophages in the brain, are responsible for immune responses and synaptic remodeling. Although the function of microglia is regulated by circadian rhythms, it is still unclear whether microglia are involved in the generation and light entrainment of circadian rhythms of behavior. Here, we report that microglial depletion does not alter behavioral circadian rhythms. We depleted ~ 95% of microglia in the mouse brain by PLX3397, a CSF1R inhibitor, and analyzed the effect on the spontaneous behaviors of mice. We found that neither the free-running period under constant darkness nor light entrainment under jet-lag circumstances were influenced by the ablation of microglia. Our results demonstrate that the circadian rhythms of locomotor activity, an important output of the circadian clock in the brain, are likely a phenomenon not produced by microglia.

DOI： 10.1186/s13041-023-01021-1

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.neures.2023.01.011

Web of Science

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Society of Toxicology  

<p>Methyl vinyl ketone (MVK) is an environmental hazardous substrate which is mainly present in cigarette smoke, industrial waste, and exhaust gas. Despite many chances to be exposed to MVK, the cellular toxicity of MVK is largely unknown. Neurons are the main component of the brain, which is one the most vital organs to human beings. Nevertheless, the influence of MVK to neurons has not been investigated. Here, we determined whether MVK treatment negatively affects neuronal survival and axonal morphogenesis using primary hippocampal neuronal cultures. We treated hippocampal neurons with 0.1 μM to 3.0 μM MVK and observed a concentration-dependent increase of neuronal death rate. We also demonstrated that the treatment with a low concentration of MVK 0.1 μM or 0.3 μM inhibited axonal branching specifically without affecting axon outgrowth. Our results suggest that MVK is highly toxic to neurons.</p>

DOI： 10.2131/jts.47.375

Web of Science

Scopus

PubMed

CiNii Research

researchmap

Language：Japanese   Publisher：Japanese Pharmacological Society  

<p>Most animal species sleep, from invertebrates to primates. We describe the electrophysiological hallmarks of sleep in reptiles. Recordings from the brains of Australian dragon <i>Pogona vitticeps</i> revealed the typical features of slow-wave sleep and rapid eye movement (REM) sleep, suggesting that dragons can be a useful model for studying these sleep stages. In this presentation, I will focus on the claustrum. The mammalian claustrum, owing to its widespread connectivity with other forebrain structures, has been hypothesized to mediate functions ranging from decision making to consciousness. We report that a homolog of the claustrum, identified by single-cell transcriptomics and viral tracing of connectivity, exists also in reptiles. There, it underlies the generation of sharp-waves during slow-wave sleep. The sharp-waves, together with superimposed high-frequency ripples, propagate to the entire forebrain. It is also characterized by converging input from mid- and hind-brain areas involved in wake/sleep control. Periodic modulation of serotonin concentration in claustrum, for example, imposes a matching modulation of sharp-wave production. The claustrum is therefore an ancient brain structure, with a potentially important role in the widespread control of brain states due to its divergent projections to the forebrain and its role in sharp-wave generation during slow-wave sleep.</p>

DOI： 10.1254/jpssuppl.94.0_1-p1-42

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

Hippocampal neurons play a crucial role in memory formation. Accumulating evidence raises the possibility that hippocampal sharp-wave ripples (SW-Rs) are involved in memory consolidation. Here, we examined in an animal model of diabetes and found the amplitude of SW-Rs in diabetic mice were smaller than control group and were rescued by acute application of l-lactate, a major neural energy source. The cognitive impairment in diabetic mice was alleviated by intracerebroventricular l-lactate treatment. Our results suggested that l-lactate is important for hippocampal dysfunction in diabetes.

DOI： 10.1016/j.jphs.2019.09.004

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: A method that promotes the retrieval of lost long-term memories has not been well established. Histamine in the central nervous system is implicated in learning and memory, and treatment with antihistamines impairs learning and memory. Because histamine H3 receptor inverse agonists upregulate histamine release, the inverse agonists may enhance learning and memory. However, whether the inverse agonists promote the retrieval of forgotten long-term memory has not yet been determined. METHODS: Here, we employed multidisciplinary methods, including mouse behavior, calcium imaging, and chemogenetic manipulation, to examine whether and how the histamine H3 receptor inverse agonists, thioperamide and betahistine, promote the retrieval of a forgotten long-term object memory in mice. In addition, we conducted a randomized double-blind, placebo-controlled crossover trial in healthy adult participants to investigate whether betahistine treatment promotes memory retrieval in humans. RESULTS: The treatment of H3 receptor inverse agonists induced the recall of forgotten memories even 1 week and 1 month after training in mice. The memory recovery was mediated by the disinhibition of histamine release in the perirhinal cortex, which activated the histamine H2 receptor. Histamine depolarized perirhinal cortex neurons, enhanced their spontaneous activity, and facilitated the reactivation of behaviorally activated neuronal ensembles. A human clinical trial revealed that treatment of H3 receptor inverse agonists is specifically more effective for items that are more difficult to remember and subjects with poorer performance. CONCLUSIONS: These results highlight a novel interaction between the central histamine signaling and memory engrams.

DOI： 10.1016/j.biopsych.2018.11.009

Web of Science

Scopus

PubMed

researchmap

Language：English   Publisher：Japanese Pharmacological Society  

<p>Even after memories fade over long time, the lost memories may persist latently in the brain. Reinforcement of positive modulators for retrieval of long-term memory may recover the ostensibly forgotten items. However, how the retrieval of long-term memory is modulated is less understood than short-term memory. Thus, a method that promotes the retrieval of forgotten long-term memories has not been well established. Central histamine is implicated in learning and memory. Histamine H3 receptors inhibit the presynaptic release of histamine and other neurotransmitters and negatively regulate histamine synthesis. Because histamine H3 receptors are constitutively active, their inverse agonists upregulate histamine release. Therefore, histamine H3 receptor inverse agonists may enhance learning and memory. In this study, we examined whether histamine H3 receptor inverse agonists enhance retrieval of long-term memory and recover the forgotten long-term memory in mice and humans.</p><p>We employed the novel object recognition task, wherein the test session mice were presented with a novel and a familiar object that was presented during the training session. A single treatment of histamine H3 receptor inverse agonists (thioperamide and betahistine) followed by memory retrieval tests restored forgotten object recognition memories in mice. The treatment induced the recall of forgotten memories even 1 week and 1 month after training. Activation of histamine receptor signaling in the perirhinal cortex (PRh) was critical for thioperamide-induced memory recovery because intraperitoneal thioperamide treatment increased PRh histamine release, and intra-PRh injection of ranitidine (H2 receptor antagonist) blocked the thioperamide-induced memory recovery. In neuronal and neuronal circuit levels, histamine depolarized PRh neurons, enhanced their spontaneous activity, and facilitated the reactivation of behaviorally activated neurons. Chemogenetically increased spontaneous activity in the PRh was sufficient for the memory recovery. Moreover, in a human clinical trial, betahistine treatment enhanced retrieval of object recognition memory. The enhancement of memory retrieval was more evident for items that are more difficult to remember and subjects with poorer performance. Betahistine treatment did not alter working memory or attention.</p><p>In conclusion, our findings indicate that activation of histamine receptor signaling in the PRh boosts reactivation of weak memory engrams and restores the apparently forgotten memories.</p>

DOI： 10.1254/jpssuppl.wcp2018.0_po1-1-11

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

Our group has recently reported that in the immortal human HepG2 liver cell line, sphingosine 1‑phosphate (S1P) increases transcription of plasminogen activator inhibitor type‑1 (PAI‑1), the major physiological inhibitor of fibrinolysis, within 4 h. The present study aimed to elucidate the molecular mechanisms underlying this effect. PAI‑1 expression was measured by reverse transcription‑quantitative polymerase chain reaction and immunoblotting. It was demonstrated that S1P increased PAI‑1 promoter activity but did not increase the activity of promoters lacking the hypoxia responsive element (HRE) 2. In addition, S1P transiently increased the concentration of hypoxia inducible factor (HIF)‑1α, a transcription factor capable of binding to HRE. When HIF‑1α was knocked down, the induction of transcription of PAI‑1 by S1P was no longer observed. Sphingosine kinase (SPHK) activity is increased by hypoxia. It was demonstrated that increases in the concentration of the HIF‑1α protein induced by hypoxia were prevented by treatment with SPHK inhibitor or S1P receptor antagonists. Thus, modification of the induction of HIF‑1α by S1P, leading to increased transcription of PAI‑1, may be an attractive therapeutic target for thrombosis and consequent inhibition of fibrinolysis associated with hypoxia.

DOI： 10.3892/mmr.2016.5451

Scopus

PubMed

J-GLOBAL

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Calcium imaging has become a fundamental modality for studying neuronal circuit dynamics both in vitro and in vivo. However, identifying calcium events (CEs) from spectral data remains laborious and difficult, especially since the signal-to-noise ratio (SNR) often falls below 2. Existing automated signal detection methods are generally applied at high SNRs, leaving a large need for an automated algorithm that can accurately extract CEs from fluorescence intensity data of SNR 2 and below. NEW METHOD: In this work we develop a Matched filter for Multi-unit Calcium Event (MMiCE) detection to extract CEs from fluorescence intensity traces of simulated and experimentally recorded neuronal calcium imaging data. RESULTS: MMiCE reached perfect performance on simulated data with SNR ≥ 2 and a true positive (TP) rate of 98.27% (± 1.38% with a 95% confidence interval), and a false positive(FP) rate of 6.59% (± 2.56%) on simulated data with SNR 0.2. On real data, verified by patch-clamp recording, MMiCE performed with a TP rate of 100.00% (± 0.00) and a FP rate of 2.04% (± 4.10). COMPARISON WITH EXISTING METHOD(S): This high level of performance exceeds existing methods at SNRs as low as 0.2, which are well below those used in previous studies (SNR ≃ 5-10). CONCLUSION: Overall, the MMiCE detector performed exceptionally well on both simulated data, and experimentally recorded neuronal calcium imaging data. The MMiCE detector is accurate, reliable, well suited for wide-spread use, and freely available at sites.uci.edu/aggies or from the corresponding author.

DOI： 10.1016/j.jneumeth.2015.10.014

PubMed

J-GLOBAL

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Spontaneous neuronal activity is present in virtually all brain regions, but neither its function nor spatiotemporal patterns are fully understood. Ex vivo organotypic slice cultures may offer an opportunity to investigate some aspects of spontaneous activity, because they self-restore their networks that collapsed during slicing procedures. In hippocampal networks, we compared the levels and patterns of in vivo spontaneous activity to those in acute and cultured slices. We found that the firing rates and excitatory synaptic activity in the in vivo hippocampus are more similar to those in slice cultures compared to acute slices. The soft confidence-weighted algorithm, a machine learning technique without human bias, also revealed that hippocampal slice cultures resemble the in vivo hippocampus in terms of the overall tendency of the parameters of spontaneous activity.

DOI： 10.1007/s12576-014-0337-4

PubMed

J-GLOBAL

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：8  

Hippocampal sharp wave (SW)/ripple complexes are thought to contribute to memory consolidation. Previous studies suggest that behavioral rewards facilitate SW occurrence in vivo. However, little is known about the precise mechanism underlying this enhancement. Here, we examined the effect of dopaminergic neuromodulation on spontaneously occurring SWs in acute hippocampal slices. Local field potentials were recorded from the CA1 region. A brief (1 min) treatment with dopamine led to a persistent increase in the event frequency and the magnitude of SWs. This effect lasted at least for our recording period of 45 min and did not occur in the presence of a dopamine D1/D5 receptor antagonist. Functional multineuron calcium imaging revealed that dopamine-induced SW augmentation was associated with an enriched repertoire of the firing patterns in SW events, whereas the overall tendency of individual neurons to participate in SWs and the mean number of cells participating in a single SW were maintained. Therefore, dopaminergic activation is likely to reorganize cell assemblies during SWs.

DOI： 10.1371/journal.pone.0104438

PubMed

J-GLOBAL

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：3  

Correlated spiking activity prevails in immature cortical networks and is believed to contribute to neuronal circuit maturation; however, its spatiotemporal organization is not fully understood. Using wide-field calcium imaging from acute whole-brain slices of rat pups on postnatal days 1-6, we found that correlated spikes were initiated in the anterior part of the lateral entorhinal cortex and propagated anteriorly to the frontal cortex and posteriorly to the medial entorhinal cortex, forming traveling waves that engaged almost the entire cortex. The waves were blocked by ionotropic glutamatergic receptor antagonists but not by GABAergic receptor antagonists. During wave events, glutamatergic and GABAergic synaptic inputs were balanced and induced UP state-like depolarization. Magnified monitoring with cellular resolution revealed that the layer III neurons were first activated when the waves were initiated. Consistent with this finding, layer III contained a larger number of neurons that were autonomously active, even under a blockade of synaptic transmission. During wave propagation, the layer III neurons constituted a leading front of the wave. The waves did not enter the parasubiculum; however, in some cases, they were reflected at the parasubicular border and propagated back in the opposite direction. During this reflection process, the layer III neurons in the medial entorhinal cortex maintained persistent activity. Thus, our data emphasize the role of layer III in early network behaviors and provide insight into the circuit mechanisms through which cerebral cortical networks maturate.

DOI： 10.1523/JNEUROSCI.2522-12.2013

PubMed

J-GLOBAL

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Sharp wave-ripple complexes (SW-Rs), a transient form of high-frequency field oscillations observed in the hippocampus, are thought to mediate memory consolidation. They are initiated mainly in hippocampal CA3 area and propagate to the entorhinal cortex through the subiculum; however, little is known about how SW-Rs are initiated and propagate. Here, we used functional multineuronal calcium imaging to monitor SW-R-relevant neuronal activity from the subiculum at single-cell resolution. An unexpected finding was that a subset of subicular neurons was activated immediately before hippocampal SW-Rs. The SW-R-preceding activity was not abolished by surgical lesion of the CA1-to-subiculum projection, and thus, it probably arose from entorhinal inputs. Therefore, SW-Rs are likely to be triggered by entorhinal-to-CA3/CA1 inputs. Moreover, the subiculum is not merely a passive intermediate region that SW-Rs pass through, but rather, it seems to contribute to an active modification of neural information related to SW-Rs.

DOI： 10.1038/srep02696

PubMed

J-GLOBAL

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Cholinergic muscarinic innervations to the hippocampus play a role in learning and memory. Here we report that pharmacological activation of muscarinic receptors eliminates sharp wave-ripple events in the mouse hippocampal CA1 region in vivo and in vitro. This effect was associated with a decorrelation of excitatory synaptic inputs and a net increase in inhibitory conductances in pyramidal neurons. Multineuron calcium imaging revealed that muscarinic activation altered the spatiotemporal pattern of network activities. Thus, cholinergic input is likely to contribute to a neuromodulatory switch of hippocampal network states, as proposed in the "two-stage" model of learning processes.

DOI： 10.1016/j.brainres.2012.04.037

PubMed

J-GLOBAL

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：2  

Cannabinoid agonists impair hippocampus-dependent learning and memory. Using mouse hippocampal slice preparations, we examined the effect of anandamide, an endogenous cannabinoid, on sharp wave-ripple (SW-R) complexes, which are believed to mediate memory consolidation during slow-wave sleep or behavioral immobility. Anandamide reduced the frequency of SW-Rs recorded from the CA3 region, and this effect was abolished by AM251, a cannabinoid CB1-receptor antagonist. We further addressed the action of anandamide using a functional multineuron calcium imaging technique. Anandamide reduced the firing rate of hippocampal neurons as well as disrupted the temporal coordination of their firings during SW-R.

DOI： 10.1254/jphs.11199FP

PubMed

researchmap