eLife
·
2025
·
IF 0
Lin Yan,Litao Wu,Timothy D Wiggin,Xiaojuan Su,Wei Yan,Hailiang Li,Lei Li,Zhonghua Lu,Yuantao Li,Zhiqiang Meng,Fang Guo,Fan Li,Leslie C Griffith,Chang Liu
Sleep disturbances are associated with poor long-term memory (LTM) formation, yet the underlying cell types and neural circuits involved have not been fully decoded. Dopamine neurons (DANs) are involved in memory processing at multiple stages. Here, using both male and female flies, Drosophila melanogaster, we show that, during the first few hours of memory consolidation, disruption of basal activity of a small subset of protocerebral anterior medial DANs (PAM-DANs), by either brief activation or inhibition of the two dorsal posterior medial (DPM) neurons, impairs 24 h LTM. Interestingly, these brief changes in activity using female flies result in sleep loss and fragmentation, especially at night. Pharmacological rescue of sleep after manipulation restores LTM. A specific subset of PAM-DANs (PAM-α1) that synapse onto DPM neurons specify the microcircuit that links sleep and memory. PAM-DANs, including PAM-α1, form functional synapses onto DPM mainly via multiple dopamine receptor subtypes. This PAM-α1 to DPM microcircuit exhibits a synchronized, transient, post-training increase in activity during the critical memory consolidation window, suggesting an effect of this microcircuit on maintaining the sleep necessary for LTM consolidation. Our results provide a new cellular and circuit basis for the complex relationship between sleep and memory.
研究领域:
神经科学
·
行为生物学
·
睡眠研究
·
记忆机制
✓ 已验证
产品关联
DOI
Neural Regeneration Research
·
2025
·
IF 6.7
Gu Xinyi,Huang Chen,Wang Shen,Deng Jin,Guo Shuhang,Yin Xiaofeng
To perform various functions in the body, skeletal muscle is controlled and coordinated as a whole by nerves. However, there has been little research into whether the nerve control characteristics of different muscles are different, and the importance of these potential differences. In the present study, we used a three-dimensional imaging of solvent-cleared organ-compatible multi-tracer technique to explore the spatial distribution patterns of sensory and sympathetic neurons that innervate limb muscles. We integrated transcriptome sequencing datasets from mouse limb muscles in public databases and performed correlation analysis with neuronal spatial distribution data to reveal the unique effects of different types of neurons on muscle functional pathways. In terms of spatial distribution patterns, sympathetic neurons exhibited a more concentrated distribution than sensory and motor neurons. In addition, the neuronal innervation of limb muscles exhibited four different characteristics: sympathetic neuron-rich muscle, sensory neuron-rich muscle, neuron-sparse muscle, and motor neuron-rich muscle. Sensory neuron density was mainly associated with muscle contractile structure and cell pH, whereas sympathetic neuron density was associated with protein kinase activity, muscle vasculature, muscle calcium-dependent protein kinase activity, lipid transport, and vesicle release. Motor neuron density was mainly associated with protein kinase activity, cell adhesion, oxidoreductase activity, and exocytosis. These findings may contribute to a deeper understanding of how nerves cooperate to endow muscles with diverse physiological functions, thereby providing new insights and experimental evidence for the treatment of various neuromuscular diseases.
研究领域:
神经科学
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肌肉生理学
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系统生物学
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分子生物学
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解剖学
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产品关联
DOI
PubMed
高影响因子
Cell Reports
·
2025
·
IF 6.9
Zijia Sun,Yingsheng Wang,Shaorui Liu,Hui Li,Danyang He,Heping Xu
Intrinsic enteric neurons (iENs) form a crucial neuronal network within the myenteric and submucosal plexus of the gastrointestinal tract, primarily responsible for regulating gut peristalsis. The mechanisms by which iENs sense and integrate dietary and microbial signals to regulate intestinal homeostasis and inflammation remain unclear. Here, we showed that environmental sensor aryl hydrocarbon receptor (AHR) was expressed in different iEN subsets in the ileum and colon and that AHR ligands differentially modulated iEN activity in these regions. Genetic perturbation of Ahr in neurons increased iEN activation in the ileum but, conversely, decreased it in the colon in response to different intestinal pathogens. Furthermore, neuronal AHR deficiency enhanced the clearance of bacterial pathogens, which was associated with increased proliferation and abundance of group 3 innate lymphoid cells in the ileum. Together, our findings demonstrate the region-specific functions of AHR in neurons in response to infections.
研究领域:
神经科学
·
免疫学
·
胃肠病学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·Vol. 11
·期 29
·2401670
·
IF 14.3
Shiya Lv,Fan Mo,Zhaojie Xu,Yu Wang,Gucheng Yang,Meiqi Han,Luyi Jing,Wei Xu,Yiming Duan,Yaoyao Liu,Ming Li,Juntao Liu,Jinping Luo,Mixia Wang,Yilin Song,Yirong Wu,Xinxia Cai
Hippocampal CA1 neurons show intense firing at specific spatial locations, modulated by isolated landmarks. However, the impact of real-world scene transitions on neuronal activity remains unclear. Moreover, long-term neural recording during movement challenges device stability. Conventional rigid-based electrodes cause inflammatory responses, restricting recording durations. Inspired by the jellyfish tentacles, the multi-conductive layer ultra-flexible microelectrode arrays (MEAs) are developed. The tentacle MEAs ensure stable recordings during movement, thereby enabling the discovery of soft boundary neurons. The soft boundary neurons demonstrate high-frequency firing that aligns with the boundaries of scene transitions. Furthermore, the localization ability of soft boundary neurons improves with more scene transition boundaries, and their activity decreases when these boundaries are removed. The innovation of ultra-flexible, high-biocompatible tentacle MEAs improves the understanding of neural encoding in spatial cognition. They offer the potential for long-term in vivo recording of neural information, facilitating breakthroughs in the understanding and application of brain spatial navigation mehanisms.
研究领域:
神经科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2016
·Vol. 6
·期 1
·1-11
·
IF 5.228
Ma Jie,Yang Qunfang,Wei Yuling,Yang Yang,Ji Chaonan,Hu Xinyue,Mai Shaoshan,Kuang Shengnan,Tian Xiaoyan,Luo Ying,Liang Guojuan,Yang Junqing
In the present study, the agonists and antagonists of DP receptor were used to examine whether the PGD 2 -DP signaling pathway affects neuronal function. Primary cultured hippocampal neuron was prepared and treated with aluminum maltolate (100 μM) to establish the neuronal damage model. PGD 2 and cAMP content was detected by ELISA. L-PGDS and DPs mRNA and protein expression were measured by RT-PCR and Western blotting, respectively. The aluminium-load neuron was treated with the DP 1 agonist BW245C, the DP 1 antagonist BWA868C, the DP 2 agonist DK-PGD 2, and the DP 2 antagonist CAY10471, respectively. Neuronal pathomorphology was observed using H-E staining. The cell viability and the lactate dehydrogenase leakage rates of neurons were measured with MTT and LDH kit, respectively. Ca 2+ level was detected by Fluo-3/AM. In the model group, the MTT values obviously decreased; LDH leakage rates and PGD 2 content increased significantly; L-PGDS, DP 1 mRNA and protein expressions increased and DP 2 level decreased. BW245C reduced the Ca 2+ fluorescence intensity and protected the neurons. DK-PGD 2 increased the intensity of Ca 2+ fluorescence, while CAY10471 had the opposite effect. In conclusion, contrary to the effect of DP 2 , the PGD 2 -DP 1 signaling pathway protects against the primary cultured rat hippocampal neuronal injury caused by aluminum overload.
研究领域:
神经科学
·
药理学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL BIOCHEMISTRY AND FUNCTION
·
2024
·Vol. 42
·期 3
·e4003
·
IF 2.8
Mengnan Xing,Xinlei Yang,Sinan Jin,Xiangping Xu
Neuronal pentraxin 2 (Nptx2), a member of the synaptic protein family linked to excitatory synaptic formation, is found to be upregulated in epileptic mice, yet its role in epilepsy has been unclear. In vivo, we constructed a mouse model of epilepsy by using kainic acid induction. In vitro experiments, a Mg 2+ -free medium was used to induce epileptiform discharges in neurons. The results showed that the Nptx2 was upregulated in epileptic mice. Moreover, Nptx2 knockdown reduced the number of seizures and seizure duration. Knocking down Nptx2 not only reduced the number and duration of seizures but also showed a decrease in electroencephalogram amplitude. Behavioral tests indicated improvements in learning and memory abilities after Nptx2 knockdown. The Nissl staining and Timms staining revealed that Nptx2 silencing mitigated epilepsy-induced brain damage. The immunofluorescence staining revealed that Nptx2 absence resulted in a reduction of apoptosis. Nptx2 knockdown reduced Bax, cleaved caspase3, and cleaved caspase9 expression, while increased Bcl-2 expression. Notably, Nptx2 knockdown inhibited GluA1 phosphorylation at the S831 site and reduced the GluA1 membrane expression. The PSD95 expression declined in the epilepsy model, while the Nptx2 knockdown reversed it. Collectively, our study indicated that Nptx2 silencing not only alleviated brain damage and neuron apoptosis but also improved learning and memory ability in epileptic mice, suggesting Nptx2 as a promising target for epilepsy treatment. Significant statement Nptx2 is associated with excitatory synaptic formation, while the role of Nptx2 in epilepsy remains unclear. Our finding indicated an upregulation of Nptx2 in epileptic mice, and knockdown of Nptx2 leading to a reduction in seizure frequency and duration, alongside improvements in learning and memory. Nptx2 knockdown alleviated neuron apoptosis. More importantly, GluA1 phosphorylation in the S831 site was increased in KA mice, while knockdown of Nptx2 reversed it. Nptx2 knockdown decreased the GluA1 membrane expression. Overall, our study suggested that Nptx2 silencing alleviated brain damage and inhibited neuron apoptosis. This study offers novel insights into epilepsy treatment.
研究领域:
神经科学
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
NEUROPHARMACOLOGY
·
2019
·
IF 4.367
Xin-Chun Zhang,Ai-Ping Gu,Chun-Ye Zheng,Ying-Bin Li,Hong-Feng Liang,Hua-Jun Wang,Xia-Lin Tang,Xiao-Xin Bai,Jun Cai
Yin-Yang 1 (YY1) has been identified as playing critical roles in multiple diseases . However, little is known regarding its roles and mechanisms in cerebral ischemia/reperfusion (I/R) injury. This study is aimed to explore the roles of YY1 in regulating neuronal apoptosis in cerebral I/R injury and its underlying mechanisms. Primary mouse cerebral cortical neurons were isolated and subjected to OGD/R to mimic cerebral I/R injury in vitro . The roles of YY1 on OGD/R-induced neuronal injury were investigated by performing western blotting , quantitative real-time polymerase chain reaction, TUNEL , RNA-binding protein immunoprecipitation , chromatin immunoprecipitation, chromatin isolation by RNA purification assay, glucose uptake assay, lactate production assay, and extracellular acidification rate assay. YY1-binding long non-coding RNAs (LncRNAs) in neurons subjected to OGD/R were identified by RIP and RNA sequencing . The roles of YY1 on cerebral I/R in vivo were detected by assessing neuronbehaviour, infarct size, and neuronal apoptosis. We found that YY1 expression is downregulated, and LncRNA GAS5 is upregulated in neurons subjected to OGD/R. OGD/R treatment promotes YY1 interacting with GAS5 in neurons, and YY1 negatively regulates GAS5 expression by binding to GAS5 promoter to repress its transcription. Besides, YY1 and GAS5 bind to the same region of PFKFB3 promoter to promote PFKFB3 expression and strengthen neuronal glycolysis, resulting in aggravating OGD/R-induced neuronal apoptosis. Knockdown of YY1 or GAS5 protects against I/R-induced ischemic brain damage and improves overall neurological functions in vivo. Overall, YY1 interacts with LncRNA GAS5 to promote PFKFB3 transcription to enhance neuronal glycolysis, resulting in aggravating cerebral I/R injury.
研究领域:
神经科学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Oncotarget
·
2017
·
IF 5.168
Lu Yang,Yuling Wei,Ying Luo,Qunfang Yang,Huan Li,Congli Hu,Yang Yang,Junqing Yang
To observe the characteristic changes of PGE 2 -EP s pathway and divergent functions of PGE 2 receptor subtypes on neuronal injury. The primary cultured rat hippocampus neuron injury model was established via aluminum maltolate (100 μM). The aluminum-overload neurons were treated with the agonists of EP1 (17-phenyl trinor Prostaglandin E2 ethyl amide), EP2 (Butaprost), EP3 (Sulprostone) and EP4 (CAY10598) and antagonists of EP1 (SC-19220), EP2 (AH6809) and EP4 (L-161982) at different concentrations, respectively. The neuronal viability, lactate dehydrogenase leakage rate and PGE2 content were detected by MTT assay, lactate dehydrogenase assay kit and enzyme-linked immunosorbent assay, respectively. The mRNA and protein expressions of mPGES-1 and EPs were determined by RT-PCR and western blot, respectively. The pathomorphology was identified by hematoxylin-eosin staining. In the model group, neuronal viability significantly decreased, while lactate dehydrogenase leakage rate and PGE2 content increased. The mPGES-1, EP1, EP2 and EP4 mRNA expression, and the mPGES-1, EP1 and EP2 protein expression increased, while EP 3 level decreased. EP3 agonist exerted protective function in neuronal viability and lactate dehydrogenase leakage rate, while EP1 agonist, EP2 and EP4 antagonist exerted an opposite effect. In conclusion, aluminum-overload caused an imbalance of PGE 2 -EP 1-4 pathway and activation of EP receptor may provide a viable therapeutic target in neuronal injury.
研究领域:
神经科学
·
药理学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
·
2022
·
IF 4.571
Jielin Tang,Jiayi Li,Qinyu Zhou,Guzailinuer Kuerban,Jinyan Qin,Hongdan Zhang,Rongli Sun,Lihong Yin,Yuepu Pu,Juan Zhang
As a new type of flame retardant , Organic Phosphate Flame Retardant has been widely used worldwide. The purpose of our research is to determine the neurotoxicity of Tris (1,3-dichloroisopropyl) phosphate (TDCPP) to Caenorhabditis elegans and its mechanism. L1 larvae wild-type C. elegans were exposed to different concentrations of TDCPP, and the effects on motor behavior (head thrashes, body bends, pumping times, chemotaxis index), ROS levels, and p38MAPK signaling pathway-related gene expression levels were measured. Three transgenic nematode strains, BZ555, DA1240, and EG1285, were also used to study the effects of TDCPP on nematode dopamine neurons, glutamate neurons, and GABA neurons. The results showed that TDCPP can inhibit the head thrashes and body bends of the nematode, reduce dopamine production, increase the level of ROS in the body, and affect the expression of genes related to the p38MAPK signaling pathway. We next employed ROS production and motor behavior as toxicity assessment endpoints to determine the involvement of p38 MAPK signaling in the regulation of response to TDCPP. The results showed that the nematodes with low expression of pmk-1 were less sensitive to the TDCPP. It was suggested that TDCPP had neurotoxicity and regulated neurotoxicity to C. elegans by activating the p38-MAPK signaling pathway. The research in this article provides important information for revealing the environmental health risks of organophosphorus flame retardants and their toxic mechanism of action.
研究领域:
毒理学
·
环境健康
·
分子生物学
·
神经科学
✓ 已验证
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2021
·Vol. 35
·期 10
·5767-5780
·
IF 5.882
Lin Zhu,Zhenchao Liu,Yuqian Ren,Xiaolin Wu,Yingjuan Liu,Tingting Wang,Yizhao Li,Yusheng Cong,Yunliang Guo
Studies have found that salidroside, isolated from Rhodiola rosea L , has various pharmacological activities, but there have been no studies on the effects of salidroside on brain hippocampal senescence. The purpose of this study was to investigate the mechanistic role of salidroside in hippocampal neuron senescence and injury. In this study, long-term cultured primary rat hippocampal neurons and naturally aged C57 mice were treated with salidroside. The results showed that salidroside increased the viability and MAP2 expression, reduced β-galactosidase (β-gal) levels of rat primary hippocampal neurons. Salidroside also improved cognition dysfunction in ageing mice and alleviated neuronal degeneration in the ageing mice CA1 region. Moreover, salidroside decreased the levels of oxidative stress and p21, p16 protein expressions of hippocampal neurons and ageing mice. Salidroside promoted telomerase reverse transcriptase (TERT) protein expression via the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway. In conclusion, our findings suggest that salidroside has the potential to be used as a therapeutic strategy for anti-ageing and ageing-related disease treatment.
研究领域:
神经科学
·
药理学
·
衰老研究
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-19
·
IF 16.6
Zhan Xu,Chen Chao,Niu Longgang,Du Xinran,Lei Ying,Dan Rui,Wang Zhao-Wen,Liu Ping
Locomotor activities can enhance learning, but the underlying circuit and synaptic mechanisms are largely unknown. Here we show that locomotion facilitates aversive olfactory learning in C. elegans by activating mechanoreceptors in motor neurons, and transmitting the proprioceptive information thus generated to locomotion interneurons through antidromic-rectifying gap junctions. The proprioceptive information serves to regulate experience-dependent activities and functional coupling of interneurons that process olfactory sensory information to produce the learning behavior. Genetic destruction of either the mechanoreceptors in motor neurons, the rectifying gap junctions between the motor neurons and locomotion interneurons, or specific inhibitory synapses among the interneurons impairs the aversive olfactory learning. We have thus uncovered an unexpected role of proprioception in a specific learning behavior as well as the circuit, synaptic, and gene bases for this function.
研究领域:
神经科学
·
分子生物学
·
行为生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NEUROSCIENCE
·
2023
·Vol. 43
·期 16
·2822-2836
·
IF 5.3
Jiao Ma,Zhechun Hu,Huimin Yue,Yujian Luo,Chao Wang,Xuan Wu,Yan Gu,Lang Wang
Metabotropic glutamate receptor 2 (GRM2) is highly expressed in hippocampal dentate granule cells (DGCs), regulating synaptic transmission and hippocampal functions. Newborn DGCs are continuously generated throughout life and express GRM2 when they are mature. However, it remained unclear whether and how GRM2 regulates the development and integration of these newborn neurons. We discovered that the expression of GRM2 in adult-born DGCs increased with neuronal development in mice of both sexes. Lack of GRM2 caused developmental defects of DGCs and impaired hippocampus-dependent cognitive functions. Intriguingly, our data showed that knockdown of Grm2 resulted in decreased b/c-Raf kinases and paradoxically led to an excessive activation of MEK/ERK1/2 pathway. Inhibition of MEK ameliorated the developmental defects caused by Grm2 knockdown. Together, our results indicate that GRM2 is necessary for the development and functional integration of newborn DGCs in the adult hippocampus through regulating the phosphorylation and activation state of MEK/ERK1/2 pathway.SIGNIFICANCE STATEMENT Metabotropic glutamate receptor 2 (GRM2) is highly expressed in mature dentate granule cells (DGCs) in the hippocampus. It remains unclear whether GRM2 is required for the development and integration of adult-born DGCs. We provided in vivo and in vitro evidence to show that GRM2 regulates the development of adult-born DGCs and their integration into existing hippocampal circuits. Lack of GRM2 in a cohort of newborn DGCs impaired object-to-location memory in mice. Moreover, we revealed that GRM2 knockdown paradoxically upregulated MEK/ERK1/2 pathway by suppressing b/c-Raf in developing neurons, which is likely a common mechanism underlying the regulation of the development of neurons expressing GRM2. Thus, Raf/MEK/ERK1/2 pathway could be a potential target for brain diseases related to GRM2 abnormality.
研究领域:
神经科学
·
分子生物学
·
发育生物学
·
认知科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）