Frontiers in Synaptic Neuroscience最新文献_第5页

Editorial: Subcellular computations and information processing. 编辑:亚细胞计算和信息处理。

IF 3.7 4区医学 Q2 NEUROSCIENCES

Frontiers in Synaptic Neuroscience

Pub Date : 2023-01-01 DOI: 10.3389/fnsyn.2023.1169671

Tomoe Ishikawa, Ayako Wendy Ishikawa, Athanasia Papoutsi, Asami Tanimura, Keisuke Yonehara

COPYRIGHT © 2023 Ishikawa, Ishikawa, Papoutsi, Tanimura and Yonehara. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Subcellular computations and information processing

引用次数: 0

Neurexins and their ligands at inhibitory synapses. 抑制性突触中的神经毒素及其配体

IF 2.8 4区医学 Q2 NEUROSCIENCES

Frontiers in Synaptic Neuroscience

Pub Date : 2022-12-21 eCollection Date: 2022-01-01 DOI: 10.3389/fnsyn.2022.1087238

Emma E Boxer, Jason Aoto

Since the discovery of neurexins (Nrxns) as essential and evolutionarily conserved synaptic adhesion molecules, focus has largely centered on their functional contributions to glutamatergic synapses. Recently, significant advances to our understanding of neurexin function at GABAergic synapses have revealed that neurexins can play pleiotropic roles in regulating inhibitory synapse maintenance and function in a brain-region and synapse-specific manner. GABAergic neurons are incredibly diverse, exhibiting distinct synaptic properties, sites of innervation, neuromodulation, and plasticity. Different classes of GABAergic neurons often express distinct repertoires of Nrxn isoforms that exhibit differential alternative exon usage. Further, Nrxn ligands can be differentially expressed and can display synapse-specific localization patterns, which may contribute to the formation of a complex trans-synaptic molecular code that establishes the properties of inhibitory synapse function and properties of local circuitry. In this review, we will discuss how Nrxns and their ligands sculpt synaptic inhibition in a brain-region, cell-type and synapse-specific manner.

自从发现神经肽（Nrxns）是重要的、进化上保守的突触粘附分子以来，人们的注意力主要集中在它们对谷氨酸能突触的功能性贡献上。最近，我们对神经肽在 GABA 能突触中的功能的认识取得了重大进展，发现神经肽可以以脑区和突触特异性的方式在调节抑制性突触的维持和功能方面发挥多向作用。GABA 能神经元种类繁多，具有不同的突触特性、神经支配部位、神经调节和可塑性。不同类别的 GABA 能神经元通常表达不同的 Nrxn 异构体，这些 Nrxn 异构体表现出不同的替代外显子用法。此外，Nrxn 配体可以不同方式表达，并显示出突触特异性定位模式，这可能有助于形成复杂的跨突触分子代码，从而确定抑制性突触功能的特性和局部电路的特性。在这篇综述中，我们将讨论 Nrxns 及其配体如何以脑区、细胞类型和突触特异性的方式形成突触抑制。

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引用次数: 0

Enhanced Non-Associative Long-Term Potentiation in Immature Granule Cells in the Dentate Gyrus of Adult Rats 成年大鼠齿状回未成熟颗粒细胞非联合长时程增强

IF 3.7 4区医学 Q2 NEUROSCIENCES

Frontiers in Synaptic Neuroscience

Pub Date : 2022-05-30 DOI: 10.3389/fnsyn.2022.889947

N. A. Simonova, M. Volgushev, A. Malyshev

The dentate gyrus is one of the few sites of neurogenesis in the adult brain. Integration of new-generated granule cells into the hippocampal circuitry provides a substrate for structural plasticity, fundamental for normal function of adult hippocampus. However, mechanisms of synaptic plasticity that mediate integration of new-generated granule cells into the existing circuitry remain poorly understood. Especially mechanisms of plasticity at GABA-ergic synapses remain elusive. Here, we show that postsynaptic spiking without presynaptic activation can induce heterosynaptic, non-associative plasticity at GABA-ergic inputs to both immature and mature granule cells. In both immature and mature neurons, plastic changes were bidirectional and individual inputs could express long-term potentiation (LTP) or long-term depression (LTD), or do not change. However, properties of non-associative plasticity dramatically change with maturation of newly generated granule cells: while in immature cells there was a clear predominance of non-associative LTP and net potentiation across the inputs, in mature neurons, potentiation and depression were balanced with no net change on average. We conclude that GABA-ergic inputs to granule cells are plastic, and that the rules for induction of non-associative plasticity change with maturation. We propose that potentiation-biased non-associative plasticity of GABA-ergic transmission might help to counter-balance an increase of excitatory drive that is facilitated by enhanced LTP at glutamatergic synapses in maturating granule cells. Such mechanism might help to build a strong GABA-ergic input to surviving active new cells, necessary for normal function of mature granule cells, which operate under a tight inhibitory control and generate sparse spiking activity.

齿状回是成人大脑中为数不多的神经发生部位之一。新生成的颗粒细胞整合到海马体回路中，为结构可塑性提供了基础，是成人海马体正常功能的基础。然而，介导新产生的颗粒细胞整合到现有电路中的突触可塑性机制仍然知之甚少。特别是gaba -能突触的可塑性机制尚不清楚。本研究表明，未激活突触前的突触后峰可以诱导未成熟和成熟颗粒细胞在gaba能输入下的异突触非联想可塑性。在未成熟和成熟神经元中，可塑性变化是双向的，个体输入可以表达长期增强(LTP)或长期抑制(LTD)，也可以不改变。然而，随着新生颗粒细胞的成熟，非联想可塑性的特性发生了显著变化:在未成熟细胞中，非联想LTP和净增强在输入中明显占优势，而在成熟神经元中，增强和抑制是平衡的，平均没有净变化。我们得出的结论是，gaba能输入颗粒细胞是可塑性的，诱导非联想可塑性的规则随着成熟而变化。我们提出，gaba能传递的增强偏倚非联想可塑性可能有助于抵消成熟颗粒细胞中谷氨酸突触LTP增强所促进的兴奋性驱动的增加。这种机制可能有助于建立一个强大的gaba能输入，以存活活跃的新细胞，这是成熟颗粒细胞正常功能所必需的，成熟颗粒细胞在严格的抑制控制下运作，产生稀疏的尖峰活动。

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引用次数: 1

Ameliorative Potential of Hot Compress on Sciatic Nerve Pain in Chronic Constriction Injury-Induced Rat Model 热敷对慢性收缩性损伤大鼠坐骨神经疼痛的改善作用

IF 3.7 4区医学 Q2 NEUROSCIENCES

Frontiers in Synaptic Neuroscience

Pub Date : 2022-05-24 DOI: 10.3389/fnsyn.2022.859278

K. Chan, W. Tsai, Chien-Yi Chiang, M. Sheu, Chih-Yang Huang, Yi-Ching Tsai, Chia-Yun Tsai, Chia-Jung Lu, Z-P Ho, D. Lai

Hot compress modalities are used to ameliorate pain despite prevalent confusion about which modality should be used and when. Most recommendations for hot compresses are based on empirical experience, with limited evidence to support its efficacy. To obtain insight into the nerve transmission mechanism of hot compresses and to identify the nerve injury marker proteins specifically associated with sciatic nerve pain, we established a rat model of chronic constriction injury (CCI) and performed mechanical allodynia, electrophysiology, and histopathological analysis. All CCI rats exhibited geometric representation of the affected hind paw, which indicated a hyper-impact on both mechanical gait and asymmetry of gait on day 28. The CCI model after 28 days of surgery significantly reduced compound muscle action potential (CMAP) amplitude, but also significantly reduced latency. Administration of hot compress for 3 weeks (heated at 40–42°C, cycle of 40 min, and rest for 20 min, three cycles each time, three times per week) significantly increased the paw withdrawal thresholds in response to stimulation by Von Frey fibers and reversed the CCI-induced reduced sciatic functional index (SFI) scores. Hot compress treatment in the CCI model improved CMAP amplitude and latency. The S100 protein expression level in the CCI+Hot compression group was 1.5-fold higher than in the CCI group; it dramatically reduced inflammation, such as tumor necrosis factor alpha and CD68 expression in nerve injury sites. Synaptophysin (Syn) expression in the CCI+Hot compression group was less than threefold in the CCI group at both nerve injury sites and brain (somatosensory cortex and hippocampus). This finding indicates that local nerve damage and inflammation cause significant alterations in the sensorimotor strip, and hot compress treatment could significantly ameliorate sciatic nerve pain by attenuating Syn and inflammatory factors from local pathological nerves to the brain. This study determines the potential efficacy and safety of hot compress, and may have important implications for its widespread use in sciatic nerve pain treatment.

热敷方式被用来减轻疼痛，尽管人们普遍对应该使用哪种方式以及何时使用感到困惑。大多数关于热敷的建议都是基于经验，支持其疗效的证据有限。为了深入了解热敷的神经传递机制，并鉴定与坐骨神经疼痛特异性相关的神经损伤标记蛋白，我们建立了慢性收缩损伤（CCI）大鼠模型，并进行了机械性异常性疼痛、电生理学和组织病理学分析。所有CCI大鼠均表现出受影响后爪的几何表现，这表明在第28天对机械步态和步态不对称性都有过度影响。手术28天后的CCI模型显著降低了复合肌肉动作电位（CMAP）幅度，但也显著降低了潜伏期。热敷3周（在40–42°C下加热，周期为40分钟，休息20分钟，每次3个周期，每周3次）显著增加了对Von Frey纤维刺激的缩爪阈值，并逆转了CCI诱导的坐骨神经功能指数（SFI）评分降低。CCI模型中的热敷治疗改善了CMAP振幅和潜伏期。CCI+热压组的S100蛋白表达水平比CCI组高1.5倍；它显著降低了神经损伤部位的炎症如肿瘤坏死因子α和CD68的表达。在神经损伤部位和大脑（体感皮层和海马体），CCI+热压组的突触肽（Syn）表达均低于CCI组的三倍。这一发现表明，局部神经损伤和炎症会导致感觉运动带发生显著改变，热敷治疗可以通过减轻从局部病理神经到大脑的Syn和炎症因子，显著改善坐骨神经疼痛。这项研究确定了热敷的潜在疗效和安全性，并可能对其在坐骨神经疼痛治疗中的广泛应用具有重要意义。

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引用次数: 1

The Yin and Yang of GABAergic and Glutamatergic Synaptic Plasticity: Opposites in Balance by Crosstalking Mechanisms. gaba能和谷氨酸能突触可塑性的阴阳:通过串扰机制平衡的对立面。

IF 3.7 4区医学 Q2 NEUROSCIENCES

Frontiers in Synaptic Neuroscience

Pub Date : 2022-05-19 eCollection Date: 2022-01-01 DOI: 10.3389/fnsyn.2022.911020

Caitlyn A Chapman, Jessica L Nuwer, Tija C Jacob

Synaptic plasticity is a critical process that regulates neuronal activity by allowing neurons to adjust their synaptic strength in response to changes in activity. Despite the high proximity of excitatory glutamatergic and inhibitory GABAergic postsynaptic zones and their functional integration within dendritic regions, concurrent plasticity has historically been underassessed. Growing evidence for pathological disruptions in the excitation and inhibition (E/I) balance in neurological and neurodevelopmental disorders indicates the need for an improved, more "holistic" understanding of synaptic interplay. There continues to be a long-standing focus on the persistent strengthening of excitation (excitatory long-term potentiation; eLTP) and its role in learning and memory, although the importance of inhibitory long-term potentiation (iLTP) and depression (iLTD) has become increasingly apparent. Emerging evidence further points to a dynamic dialogue between excitatory and inhibitory synapses, but much remains to be understood regarding the mechanisms and extent of this exchange. In this mini-review, we explore the role calcium signaling and synaptic crosstalk play in regulating postsynaptic plasticity and neuronal excitability. We examine current knowledge on GABAergic and glutamatergic synapse responses to perturbances in activity, with a focus on postsynaptic plasticity induced by short-term pharmacological treatments which act to either enhance or reduce neuronal excitability via ionotropic receptor regulation in neuronal culture. To delve deeper into potential mechanisms of synaptic crosstalk, we discuss the influence of synaptic activity on key regulatory proteins, including kinases, phosphatases, and synaptic structural/scaffolding proteins. Finally, we briefly suggest avenues for future research to better understand the crosstalk between glutamatergic and GABAergic synapses.

突触可塑性是一个关键过程，通过允许神经元根据活动的变化调整突触强度来调节神经元活动。尽管兴奋性谷氨酸能和抑制性GABA能突触后区高度接近，并且它们在树突区域内的功能整合，但同时发生的可塑性在历史上一直被低估。越来越多的证据表明，在神经和神经发育障碍中，兴奋和抑制（E/I）平衡的病理性破坏表明，需要改进对突触相互作用的更“全面”的理解。尽管抑制性长时程增强（iLTP）和抑郁（iLTD）的重要性越来越明显，但长期以来，人们仍然关注兴奋（兴奋性长时增强；eLTP）及其在学习和记忆中的作用。新出现的证据进一步表明兴奋性突触和抑制性突触之间存在动态对话，但关于这种交换的机制和程度还有很多待了解。在这篇小综述中，我们探讨了钙信号传导和突触串扰在调节突触后可塑性和神经元兴奋性中的作用。我们研究了目前关于GABA能和谷氨酸能突触对活动干扰的反应的知识，重点是短期药物治疗诱导的突触后可塑性，短期药物治疗通过神经元培养中的离子受体调节来增强或降低神经元兴奋性。为了深入研究突触串扰的潜在机制，我们讨论了突触活性对关键调节蛋白的影响，包括激酶、磷酸酶和突触结构/支架蛋白。最后，我们简要地提出了未来研究的途径，以更好地理解谷氨酸能和GABA能突触之间的串扰。

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引用次数: 0

Dexmedetomidine and Ketamine Attenuated Neuropathic Pain Related Behaviors via STING Pathway to Induce ER-Phagy 右美托咪定和氯胺酮通过STING途径诱导er吞噬减轻神经性疼痛相关行为

IF 3.7 4区医学 Q2 NEUROSCIENCES

Frontiers in Synaptic Neuroscience

Pub Date : 2022-05-13 DOI: 10.3389/fnsyn.2022.891803

Yongda Liu, Shihui Kuai, M. Ding, Zhibin Wang, Limei Zhao, P. Zhao

Our previous work indicated that ER-phagy level had altered in spinal nerve ligation (SNL) rats. In this study, we investigated whether dexmedetomidine or ketamine exhibits anti-anxiety or anti-nociceptive effects via modulation of the spinal STING/TBK pathway to alter ER-phagy in SNL rats. We evaluated the analgesic and anti-anxiety effects of ketamine and dexmedetomidine in SNL rats. 2’3’-cGAMP (a STING pathway agonist) was administrated to investigate whether enhanced spinal STING pathway activation could inhibit dexmedetomidine or ketamine treatment effects in SNL rats. Analgesic effects were assessed with the mechanical withdrawal threshold (MWT) and anti-anxiety effects were measured via an open field test (OFT). Protein expression levels were evaluated by immunoblotting. Distribution and cellular localization of Grp78 (ER stress marker) were evaluated by confocal immunofluorescence. SNL induced mechanical hypersensitivity and anxiety in rats; dexmedetomidine and ketamine both provided analgesia and anti-anxiety effects in SNL rats. Furthermore, the STING pathway was involved in the modulation of ER stress and ER-phagy in SNL rats and dexmedetomidine and ketamine alleviated ER stress by inhibiting STING pathway to enhance ER-phagy. Thus, both ketamine and dexmedetomidine provided anti-anxiety and anti-nociceptive effects by alleviating ER stress through the inhibition of the STING/TBK pathway to modulate spinal ER-phagy in SNL rats.

我们之前的研究表明，脊髓神经结扎(SNL)大鼠er吞噬水平发生了改变。在这项研究中，我们研究了右美托咪定或氯胺酮是否通过调节脊髓STING/TBK通路来改变SNL大鼠的er吞噬而表现出抗焦虑或抗伤害作用。我们评价氯胺酮和右美托咪定对SNL大鼠的镇痛和抗焦虑作用。我们给药2’3’-cGAMP(一种STING通路激动剂)来研究增强脊髓STING通路激活是否能抑制右美托咪定或氯胺酮对SNL大鼠的治疗效果。采用机械戒断阈值(MWT)评估镇痛作用，通过开放场试验(OFT)测量抗焦虑作用。免疫印迹法检测蛋白表达水平。共聚焦免疫荧光法检测内质网应激标志物Grp78的分布和细胞定位。SNL诱导大鼠机械超敏反应和焦虑;右美托咪定和氯胺酮对SNL大鼠均有镇痛和抗焦虑作用。此外，STING通路参与了SNL大鼠内质网应激和ER吞噬的调节，右美托咪定和氯胺酮通过抑制STING通路增强ER吞噬来减轻内质网应激。因此，氯胺酮和右美托咪定均通过抑制STING/TBK通路调节SNL大鼠脊髓ER吞噬，减轻内质网应激，具有抗焦虑和抗伤害作用。

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引用次数: 5

Presynaptic Mitochondria Communicate With Release Sites for Spatio-Temporal Regulation of Exocytosis at the Motor Nerve Terminal 突触前线粒体与释放位点通讯，以调控运动神经末梢的胞吐

IF 3.7 4区医学 Q2 NEUROSCIENCES

Frontiers in Synaptic Neuroscience

Pub Date : 2022-05-12 DOI: 10.3389/fnsyn.2022.858340

Mario López-Manzaneda, Andrea Fuentes-Moliz, L. Tabares

Presynaptic Ca2+ regulation is critical for accurate neurotransmitter release, vesicle reloading of release sites, and plastic changes in response to electrical activity. One of the main players in the regulation of cytosolic Ca2+ in nerve terminals is mitochondria, which control the size and spread of the Ca2+ wave during sustained electrical activity. However, the role of mitochondria in Ca2+ signaling during high-frequency short bursts of action potentials (APs) is not well known. Here, we studied spatial and temporal relationships between mitochondrial Ca2+ (mCa2+) and exocytosis by live imaging and electrophysiology in adult motor nerve terminals of transgenic mice expressing synaptophysin-pHluorin (SypHy). Our results show that hot spots of exocytosis and mitochondria are organized in subsynaptic functional regions and that mitochondria start to uptake Ca2+ after a few APs. We also show that mitochondria contribute to the regulation of the mode of fusion (synchronous and asynchronous) and the kinetics of release and replenishment of the readily releasable pool (RRP) of vesicles. We propose that mitochondria modulate the timing and reliability of neurotransmission in motor nerve terminals during brief AP trains.

突触前Ca2+调节对于准确的神经递质释放，释放位点的囊泡重新加载以及响应电活动的塑性变化至关重要。神经末梢胞质Ca2+调节的主要参与者之一是线粒体，它在持续电活动期间控制Ca2+波的大小和传播。然而，线粒体在高频短脉冲动作电位(APs)中Ca2+信号传导中的作用尚不清楚。在这里，我们通过实时成像和电生理研究了表达synaptophysin-pHluorin (SypHy)的转基因小鼠成年运动神经末梢线粒体Ca2+ (mCa2+)与胞外分泌的时空关系。我们的研究结果表明，胞吐和线粒体的热点是在亚突触功能区组织的，线粒体在几次ap后开始摄取Ca2+。我们还表明，线粒体有助于调节融合模式(同步和异步)以及囊泡易释放池(RRP)的释放和补充动力学。我们认为线粒体在短暂的AP训练中调节运动神经末梢神经传递的时间和可靠性。

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引用次数: 4

Different Synaptic Plasticity After Physiological and Psychological Stress in the Anterior Insular Cortex in an Observational Fear Mouse Model 观察性恐惧小鼠模型中前岛皮质生理和心理应激后突触可塑性的差异

IF 3.7 4区医学 Q2 NEUROSCIENCES

Frontiers in Synaptic Neuroscience

Pub Date : 2022-05-11 DOI: 10.3389/fnsyn.2022.851015

Wenlong Shi, Yuan Fu, Tian-yao Shi, Wenxia Zhou

Post-traumatic stress disorder (PTSD) can be triggered not only in people who have personally experienced traumatic events but also in those who witness them. Physiological and psychological stress can have different effects on neural activity, but little is known about the underlying mechanisms. There is ample evidence that the insular cortex, especially the anterior insular cortex (aIC), is critical to both the sensory and emotional experience of pain. It is therefore worthwhile to explore the effects of direct and indirect stress on the synaptic plasticity of the aIC. Here, we used a mouse model of observational fear to mimic direct suffering (Demonstrator, DM) and witnessing (Observer, OB) of traumatic events. After observational fear training, using a 64-channel recording system, we showed that both DM and OB mice exhibited a decreased ratio of paired-pulse with intervals of 50 ms in the superficial layers of the aIC but not in the deep layers. We found that theta-burst stimulation (TBS)–induced long-term potentiation (LTP) in OB mice was significantly higher than in DM mice, and the recruitment of synaptic responses occurred only in OB mice. Compared with naive mice, OB mice showed stronger recruitment and higher amplitude in the superficial layers of the aIC. We also used low-frequency stimulation (LFS) to induce long-term depression (LTD). OB mice showed greater LTD in both the superficial and deep layers of the aIC than naive mice, but no significant difference was found between OB and DM mice. These results provide insights into the changes in synaptic plasticity in the aIC after physiological and psychological stress, and suggest that different types of stress may have different mechanisms. Furthermore, identification of the possible causes of the differences in stress could help treat stress-related disorders.

创伤后应激障碍(PTSD)不仅会发生在亲身经历过创伤事件的人身上，也会发生在亲眼目睹这些事件的人身上。生理和心理压力对神经活动有不同的影响，但对其潜在机制知之甚少。有充分的证据表明，岛叶皮质，尤其是前岛叶皮质(aIC)，对疼痛的感觉和情感体验都至关重要。因此，直接应激和间接应激对aIC突触可塑性的影响值得进一步探讨。在这里，我们使用观察性恐惧的小鼠模型来模拟创伤事件的直接痛苦(演示者，DM)和目击(观察者，OB)。在观察恐惧训练后，采用64通道记录系统，我们发现DM和OB小鼠在aIC的浅层中出现间隔50 ms的成对脉冲比率下降，而在深层中则没有。我们发现β -爆发刺激(TBS)诱导的长期增强(LTP)在OB小鼠中显著高于DM小鼠，并且突触反应的募集仅发生在OB小鼠中。与幼稚小鼠相比，OB小鼠在aIC浅层表现出更强的招募和更高的振幅。我们还使用低频刺激(LFS)诱导长期抑郁(LTD)。OB小鼠aIC浅层和深层的LTD均高于幼稚小鼠，但OB与DM小鼠之间无显著差异。这些结果揭示了生理和心理应激后aIC突触可塑性的变化，并提示不同类型的应激可能有不同的机制。此外，确定压力差异的可能原因有助于治疗压力相关疾病。

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引用次数: 2

Selective Recruitment of Presynaptic and Postsynaptic Forms of mGluR-LTD 突触前和突触后mGluR-LTD的选择性募集

IF 3.7 4区医学 Q2 NEUROSCIENCES

Frontiers in Synaptic Neuroscience

Pub Date : 2022-05-09 DOI: 10.3389/fnsyn.2022.857675

Thomas M. Sanderson, Liam Ralph, M. Amici, Ai Na Ng, B. Kaang, M. Zhuo, S. Kim, J. Georgiou, G. Collingridge

In area CA1 of the hippocampus, long-term depression (LTD) can be induced by activating group I metabotropic glutamate receptors (mGluRs), with the selective agonist DHPG. There is evidence that mGluR-LTD can be expressed by either a decrease in the probability of neurotransmitter release [P(r)] or by a change in postsynaptic AMPA receptor number. However, what determines the locus of expression is unknown. We investigated the expression mechanisms of mGluR-LTD using either a low (30 μM) or a high (100 μM) concentration of (RS)-DHPG. We found that 30 μM DHPG generated presynaptic LTD that required the co-activation of NMDA receptors, whereas 100 μM DHPG resulted in postsynaptic LTD that was independent of the activation of NMDA receptors. We found that both forms of LTD occur at the same synapses and that these may constitute the population with the lowest basal P(r). Our results reveal an unexpected complexity to mGluR-mediated synaptic plasticity in the hippocampus.

在海马CA1区，在选择性激动剂DHPG的作用下，激活I组代谢性谷氨酸受体(mGluRs)可诱导长期抑郁(LTD)。有证据表明，mGluR-LTD可以通过神经递质释放概率的降低[P(r)]或突触后AMPA受体数量的变化来表达。然而，是什么决定了表达位点是未知的。我们使用低(30 μM)和高(100 μM)浓度的(RS)-DHPG来研究mGluR-LTD的表达机制。我们发现30 μM DHPG产生的突触前LTD需要NMDA受体的共同激活，而100 μM DHPG产生的突触后LTD不依赖于NMDA受体的激活。我们发现这两种形式的LTD发生在相同的突触上，这些可能构成了最低基础P(r)的群体。我们的研究结果揭示了mglur介导的海马突触可塑性的意想不到的复杂性。

引用次数: 3

Editorial: The Emerging Role of Endocannabinoids in Synaptic Plasticity, Reward, and Addiction 社论：内源性大麻素在突触可塑性、奖赏和成瘾中的新作用

IF 3.7 4区医学 Q2 NEUROSCIENCES

Frontiers in Synaptic Neuroscience

Pub Date : 2022-05-09 DOI: 10.3389/fnsyn.2022.898090

J. G. Edwards, L. Cristino, Dan P Covey

Endocannabinoids (eCBs) are lipid-signaling molecules that often work in a retrograde fashion. Themost common eCBs are 2-arachidonoylglycerol (2-AG) and anandamide, which bind receptors such as cannabinoid receptor 1 (CB1) and CB2. Endocannabinoid signaling controls synaptic transmission throughout the central nervous system, and is important in modulating activity and behavior in the mesolimbic reward circuit, including the ventral tegmental area (VTA), nucleus accumbens (NAc), and lateral habenula (LHb). In these regions, the eCB system is essential for normal reward learning and for some maladaptive behaviors underlying drug abuse and addiction. Recently identified lipid-signaling eCB-like molecules are also now understood to shape mesolimbic system function and reward-related behaviors. Further elucidating how the eCB system contributes to reward and addiction is especially pertinent given the recent legalization ofmedicinal or recreationalmarijuana throughout the world. Themajor psychoactive component inmarijuana is1-9-tetrahydrocannabinol (THC), which binds CB1. Common effects of THC are short-termmemory loss, appetite stimulation, and reward. There is still much to investigate concerning THC use, particularly the impact of adolescent use, with a focus on long-term alterations in eCB system function and behavioral changes. Further research is required to clarify the role of the endogenous eCB system, and the effect of exogenous CB1 or CB2targeting drugs on mesolimbic function, including synaptic plasticity, to support reward behaviors and addiction. This Research Topic focuses on endogenous eCB system function in the mesolimbic circuit with an emphasis on synaptic plasticity, reward behavior, novel eCB-like molecules, and pain.

内源性大麻素（eCBs）是脂质信号分子，通常以逆行方式工作。最常见的eCBs是2-花生酰甘油（2-AG）和阿那达明，它们结合受体，如大麻素受体1（CB1）和CB2。内源性大麻素信号控制整个中枢神经系统的突触传递，并在调节中边缘奖赏回路的活动和行为中发挥重要作用，包括腹侧被盖区（VTA）、伏隔核（NAc）和外侧缰核（LHb）。在这些地区，eCB系统对于正常的奖励学习以及药物滥用和成瘾背后的一些不适应行为至关重要。最近鉴定的脂质信号传导eCB样分子现在也被理解为塑造中边缘系统功能和奖励相关行为。鉴于最近世界各地的医用或娱乐大麻合法化，进一步阐明eCB系统如何促进奖励和成瘾尤其重要。大麻的主要精神活性成分是-9-四氢大麻酚（THC），它能结合CB1。四氢大麻酚的常见影响是短期记忆丧失、食欲刺激和奖励。关于四氢大麻酚的使用，特别是青少年使用的影响，还有很多需要研究，重点是eCB系统功能和行为变化的长期改变。需要进一步的研究来阐明内源性eCB系统的作用，以及外源性CB1或CB2靶向药物对中边缘功能的影响，包括突触可塑性，以支持奖励行为和成瘾。本研究主题关注中边缘回路中的内源性eCB系统功能，重点关注突触可塑性、奖励行为、新型eCB样分子和疼痛。

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引用次数: 0