Frontiers in Synaptic Neuroscience最新文献

{"title":"SHANK3 Antibody Validation: Differential Performance in Western Blotting, Immunocyto- and Immunohistochemistry.","authors":"Anne-Kathrin Lutz,&nbsp;Helen Friedericke Bauer,&nbsp;Valentin Ioannidis,&nbsp;Michael Schön,&nbsp;Tobias M Boeckers","doi":"10.3389/fnsyn.2022.890231","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.890231","url":null,"abstract":"<p><p>SHANK3 is a scaffolding protein implicated in autism spectrum disorders (ASD). Its function at excitatory glutamatergic synapses has been studied for the last two decades, however, tissue-specific expression patterns as well as its subcellular localization need to be studied in further detail. Especially the close sequence homology of SHANK3 to its protein family members SHANK2 and SHANK1 raises the emerging need for specific antibodies that are validated for the desired methodology. With this study, we aim to validate a set of commercial as well as homemade SHANK3 antibodies in Western Blotting, and synaptic immunocyto- and immunohistochemistry. We found that only a small subset of the antibodies included in this study meet the criteria of quality and specificity. Therefore, we aim to share our findings on SHANK3 antibody validation but also raise awareness of the necessity of antibody specificity testing in the field.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":"890231"},"PeriodicalIF":3.7,"publicationDate":"2022-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40224765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Non-Associative Long-Term Potentiation in Immature Granule Cells in the Dentate Gyrus of Adult Rats","authors":"N. A. Simonova, M. Volgushev, A. Malyshev","doi":"10.3389/fnsyn.2022.889947","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.889947","url":null,"abstract":"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.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2022-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48194037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ameliorative Potential of Hot Compress on Sciatic Nerve Pain in Chronic Constriction Injury-Induced Rat Model","authors":"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","doi":"10.3389/fnsyn.2022.859278","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.859278","url":null,"abstract":"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.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2022-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43155074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Yin and Yang of GABAergic and Glutamatergic Synaptic Plasticity: Opposites in Balance by Crosstalking Mechanisms.","authors":"Caitlyn A Chapman, Jessica L Nuwer, Tija C Jacob","doi":"10.3389/fnsyn.2022.911020","DOIUrl":"10.3389/fnsyn.2022.911020","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 ","pages":"911020"},"PeriodicalIF":3.7,"publicationDate":"2022-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9160301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9073317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dexmedetomidine and Ketamine Attenuated Neuropathic Pain Related Behaviors via STING Pathway to Induce ER-Phagy","authors":"Yongda Liu, Shihui Kuai, M. Ding, Zhibin Wang, Limei Zhao, P. Zhao","doi":"10.3389/fnsyn.2022.891803","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.891803","url":null,"abstract":"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.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2022-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48869886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Presynaptic Mitochondria Communicate With Release Sites for Spatio-Temporal Regulation of Exocytosis at the Motor Nerve Terminal","authors":"Mario López-Manzaneda, Andrea Fuentes-Moliz, L. Tabares","doi":"10.3389/fnsyn.2022.858340","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.858340","url":null,"abstract":"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.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2022-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45027014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Different Synaptic Plasticity After Physiological and Psychological Stress in the Anterior Insular Cortex in an Observational Fear Mouse Model","authors":"Wenlong Shi, Yuan Fu, Tian-yao Shi, Wenxia Zhou","doi":"10.3389/fnsyn.2022.851015","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.851015","url":null,"abstract":"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.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2022-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47137046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective Recruitment of Presynaptic and Postsynaptic Forms of mGluR-LTD","authors":"Thomas M. Sanderson, Liam Ralph, M. Amici, Ai Na Ng, B. Kaang, M. Zhuo, S. Kim, J. Georgiou, G. Collingridge","doi":"10.3389/fnsyn.2022.857675","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.857675","url":null,"abstract":"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.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2022-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41411082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: The Emerging Role of Endocannabinoids in Synaptic Plasticity, Reward, and Addiction","authors":"J. G. Edwards, L. Cristino, Dan P Covey","doi":"10.3389/fnsyn.2022.898090","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.898090","url":null,"abstract":"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.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2022-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42234825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular Strategies for Frequency-Dependent Computation of Interaural Time Difference","authors":"Rei Yamada, H. Kuba","doi":"10.3389/fnsyn.2022.891740","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.891740","url":null,"abstract":"Binaural coincidence detection is the initial step in encoding interaural time differences (ITDs) for sound-source localization. In birds, neurons in the nucleus laminaris (NL) play a central role in this process. These neurons receive excitatory synaptic inputs on dendrites from both sides of the cochlear nucleus and compare their coincidences at the soma. The NL is tonotopically organized, and individual neurons receive a pattern of synaptic inputs that are specific to their tuning frequency. NL neurons differ in their dendritic morphology along the tonotopic axis; their length increases with lower tuning frequency. In addition, our series of studies have revealed several frequency-dependent refinements in the morphological and biophysical characteristics of NL neurons, such as the amount and subcellular distribution of ion channels and excitatory and inhibitory synapses, which enable the neurons to process the frequency-specific pattern of inputs appropriately and encode ITDs at each frequency band. In this review, we will summarize these refinements of NL neurons and their implications for the ITD coding. We will also discuss the similarities and differences between avian and mammalian coincidence detectors.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2022-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42075057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}