Frontiers in Synaptic Neuroscience最新文献_第8页

Identification of Synaptic DGKθ Interactors That Stimulate DGKθ Activity. 刺激DGKθ活性的突触DGKθ相互作用物的鉴定。

IF 3.7 4区医学

Frontiers in Synaptic Neuroscience Pub Date : 2022-01-01 DOI: 10.3389/fnsyn.2022.855673

Casey N Barber, Hana L Goldschmidt, Qianqian Ma, Lauren R Devine, Robert N Cole, Richard L Huganir, Daniel M Raben

{"title":"Identification of Synaptic DGKθ Interactors That Stimulate DGKθ Activity.","authors":"Casey N Barber, Hana L Goldschmidt, Qianqian Ma, Lauren R Devine, Robert N Cole, Richard L Huganir, Daniel M Raben","doi":"10.3389/fnsyn.2022.855673","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.855673","url":null,"abstract":"Lipids and their metabolic enzymes are a critical point of regulation for the membrane curvature required to induce membrane fusion during synaptic vesicle recycling. One such enzyme is diacylglycerol kinase θ (DGKθ), which produces phosphatidic acid (PtdOH) that generates negative membrane curvature. Synapses lacking DGKθ have significantly slower rates of endocytosis, implicating DGKθ as an endocytic regulator. Importantly, DGKθ kinase activity is required for this function. However, protein regulators of DGKθ's kinase activity in neurons have never been identified. In this study, we employed APEX2 proximity labeling and mass spectrometry to identify endogenous interactors of DGKθ in neurons and assayed their ability to modulate its kinase activity. Seven endogenous DGKθ interactors were identified and notably, synaptotagmin-1 (Syt1) increased DGKθ kinase activity 10-fold. This study is the first to validate endogenous DGKθ interactors at the mammalian synapse and suggests a coordinated role between DGKθ-produced PtdOH and Syt1 in synaptic vesicle recycling.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 ","pages":"855673"},"PeriodicalIF":3.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9095502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10524767","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}

引用次数: 1

Exercise reduces the anxiogenic effects of meta-chlorophenylpiperazine: The role of 5-HT2C receptors in the bed nucleus of the stria terminalis. 运动减少间氯苯哌嗪的焦虑作用:5-HT2C受体在终纹床核中的作用。

IF 3.7 4区医学

Frontiers in Synaptic Neuroscience Pub Date : 2022-01-01 DOI: 10.3389/fnsyn.2022.1067420

James H Fox, Melissa N Boucher, Khalil S Abedrabbo, Brendan D Hare, Bethany A Grimmig, William A Falls, Sayamwong E Hammack

{"title":"Exercise reduces the anxiogenic effects of meta-chlorophenylpiperazine: The role of 5-HT2C receptors in the bed nucleus of the stria terminalis.","authors":"James H Fox, Melissa N Boucher, Khalil S Abedrabbo, Brendan D Hare, Bethany A Grimmig, William A Falls, Sayamwong E Hammack","doi":"10.3389/fnsyn.2022.1067420","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.1067420","url":null,"abstract":"Introduction: Two weeks of voluntary exercise in group-housed mice produces a reduction in anxiety-like behaviors across a number of different measures, including a reduction in the anxiety levels typically produced by the anxiogenic serotonergic drug m-chlorophenylpiperazine (mCPP), an agonist at 5-HT2C/2b receptors. We have previously demonstrated that 2-weeks of voluntary exercise blunted the anxiogenic effects of systemic mCPP, and we have also shown that mCPP infused into the bed nucleus of the stria terminalis (BNST) is anxiogenic. Here we follow up on these reports.Methods: In Experiment 1 we infused several doses of mCPP into the BNST with or without the 5-HT2C antagonist SB242084. In Experiment 2, we administered mCPP into amygdala subregions and the dorsal hippocampus to investigate site specificity. In Experiment 4 we lesioned the BNST and subsequently infused mCPP systemically, and in Experiment 4 we used RNAscope® to assess BNST 5-HT2C transcripts following wheel running.Results: BNST mCPP infusion increased acoustic startle responding, which was by 5-HT2C antagonism, while neither mCPP infused into the amygdala nor hippocampus was anxiogenic. Lesions of the BNST prevented the anxiogenic effect of systemically administered mCPP. Lastly, exercise reduced 5-HT2C transcripts in the BNST.Discussion: These results suggest that the BNST is a critical site of action for the effects of exercise on mCPP. Together these data suggest that exercise may reduce 5-HT2C receptor function in the BNST, which may, in part, explain some of the anxiolytic effects associated with wheel running.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 ","pages":"1067420"},"PeriodicalIF":3.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9880271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10585441","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}

引用次数: 1

Diverse organization of voltage-gated calcium channels at presynaptic active zones. 突触前活动区电压门控钙通道的多种组织。

IF 3.7 4区医学

Frontiers in Synaptic Neuroscience Pub Date : 2022-01-01 DOI: 10.3389/fnsyn.2022.1023256

Weijia Zhang, He-Hai Jiang, Fujun Luo

引用次数: 0

A review of the mechanisms underlying the role of the GIPC3 gene in hereditary deafness. GIPC3基因在遗传性耳聋中的作用机制综述。

IF 3.7 4区医学

Frontiers in Synaptic Neuroscience Pub Date : 2022-01-01 DOI: 10.3389/fnsyn.2022.1101587

Xinxin Li, Lin Shi, Liang Wang

引用次数: 0

Protein phosphatase-1 inhibitor-2 promotes PP1γ positive regulation of synaptic transmission. 蛋白磷酸酶-1抑制剂-2促进PP1γ正调控突触传递。

IF 3.7 4区医学

Frontiers in Synaptic Neuroscience Pub Date : 2022-01-01 DOI: 10.3389/fnsyn.2022.1021832

Karl Foley, Haider Altimimi, Hailong Hou, Yu Zhang, Cody McKee, Makaía M Papasergi-Scott, Hongtian Yang, Abigail Mayer, Nancy Ward, David M MacLean, Angus C Nairn, David Stellwagen, Houhui Xia

{"title":"Protein phosphatase-1 inhibitor-2 promotes PP1γ positive regulation of synaptic transmission.","authors":"Karl Foley, Haider Altimimi, Hailong Hou, Yu Zhang, Cody McKee, Makaía M Papasergi-Scott, Hongtian Yang, Abigail Mayer, Nancy Ward, David M MacLean, Angus C Nairn, David Stellwagen, Houhui Xia","doi":"10.3389/fnsyn.2022.1021832","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.1021832","url":null,"abstract":"Inhibitor-2 (I-2) is a prototypic inhibitor of protein phosphatase-1 (PP1), a major serine-threonine phosphatase that regulates synaptic plasticity and learning and memory. Although I-2 is a potent inhibitor of PP1 in vitro, our previous work has elucidated that, in vivo, I-2 may act as a positive regulator of PP1. Here we show that I-2 and PP1γ, but not PP1α, positively regulate synaptic transmission in hippocampal neurons. Moreover, we demonstrated that I-2 enhanced PP1γ interaction with its major synaptic scaffold, neurabin, by Förster resonance energy transfer (FRET)/Fluorescence lifetime imaging microscopy (FLIM) studies, while having a limited effect on PP1 auto-inhibitory phosphorylation. Furthermore, our study indicates that the effect of I-2 on PP1 activity in vivo is dictated by I-2 threonine-72 phosphorylation. Our work thus demonstrates a molecular mechanism by which I-2 positively regulates PP1 function in synaptic transmission.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 ","pages":"1021832"},"PeriodicalIF":3.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9582336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9444592","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}

引用次数: 0

Segregation of D1 and D2 dopamine receptors in the striatal direct and indirect pathways: An historical perspective. 纹状体直接和间接途径中D1和D2多巴胺受体的分离:历史观点。

IF 3.7 4区医学

Frontiers in Synaptic Neuroscience Pub Date : 2022-01-01 DOI: 10.3389/fnsyn.2022.1002960

Charles R Gerfen

引用次数: 9

The biological alterations of synapse/synapse formation in sepsis-associated encephalopathy. 脓毒症相关脑病中突触/突触形成的生物学改变。

IF 3.7 4区医学

Frontiers in Synaptic Neuroscience Pub Date : 2022-01-01 DOI: 10.3389/fnsyn.2022.1054605

Chuan Tang, Ye Jin, Huan Wang

{"title":"The biological alterations of synapse/synapse formation in sepsis-associated encephalopathy.","authors":"Chuan Tang, Ye Jin, Huan Wang","doi":"10.3389/fnsyn.2022.1054605","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.1054605","url":null,"abstract":"Sepsis-associated encephalopathy (SAE) is a common complication caused by sepsis, and is responsible for increased mortality and poor outcomes in septic patients. Neurological dysfunction is one of the main manifestations of SAE patients. Patients may still have long-term cognitive impairment after hospital discharge, and the underlying mechanism is still unclear. Here, we first outline the pathophysiological changes of SAE, including neuroinflammation, glial activation, and blood-brain barrier (BBB) breakdown. Synapse dysfunction is one of the main contributors leading to neurological impairment. Therefore, we summarized SAE-induced synaptic dysfunction, such as synaptic plasticity inhibition, neurotransmitter imbalance, and synapses loss. Finally, we discuss the alterations in the synapse, synapse formation, and mediators associated with synapse formation during SAE. In this review, we focus on the changes in synapse/synapse formation caused by SAE, which can further understand the synaptic dysfunction associated with neurological impairment in SAE and provide important insights for exploring appropriate therapeutic targets of SAE.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 ","pages":"1054605"},"PeriodicalIF":3.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9755596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10391559","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}

引用次数: 1

Unraveling Functional Diversity of Cortical Synaptic Architecture Through the Lens of Population Coding. 从群体编码的角度揭示皮层突触结构的功能多样性。

IF 3.7 4区医学

Frontiers in Synaptic Neuroscience Pub Date : 2022-01-01 DOI: 10.3389/fnsyn.2022.888214

Jacob L Yates, Benjamin Scholl

{"title":"Unraveling Functional Diversity of Cortical Synaptic Architecture Through the Lens of Population Coding.","authors":"Jacob L Yates, Benjamin Scholl","doi":"10.3389/fnsyn.2022.888214","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.888214","url":null,"abstract":"The synaptic inputs to single cortical neurons exhibit substantial diversity in their sensory-driven activity. What this diversity reflects is unclear, and appears counter-productive in generating selective somatic responses to specific stimuli. One possibility is that this diversity reflects the propagation of information from one neural population to another. To test this possibility, we bridge population coding theory with measurements of synaptic inputs recorded in vivo with two-photon calcium imaging. We construct a probabilistic decoder to estimate the stimulus orientation from the responses of a realistic, hypothetical input population of neurons to compare with synaptic inputs onto individual neurons of ferret primary visual cortex (V1) recorded with two-photon calcium imaging in vivo. We find that optimal decoding requires diverse input weights and provides a straightforward mapping from the decoder weights to excitatory synapses. Analytically derived weights for biologically realistic input populations closely matched the functional heterogeneity of dendritic spines imaged in vivo with two-photon calcium imaging. Our results indicate that synaptic diversity is a necessary component of information transmission and reframes studies of connectivity through the lens of probabilistic population codes. These results suggest that the mapping from synaptic inputs to somatic selectivity may not be directly interpretable without considering input covariance and highlights the importance of population codes in pursuit of the cortical connectome.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 ","pages":"888214"},"PeriodicalIF":3.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9620626","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}

引用次数: 2

Activity-Dependent Modulation of Tonic GABA Currents by Endocannabinoids in Hirudo verbana. 内源性大麻素对马鞭草强直GABA电流的活性依赖性调节。

IF 3.7 4区医学

Frontiers in Synaptic Neuroscience Pub Date : 2022-01-01 DOI: 10.3389/fnsyn.2022.760330

Riley T Paulsen, Brian D Burrell

{"title":"Activity-Dependent Modulation of Tonic GABA Currents by Endocannabinoids in Hirudo verbana.","authors":"Riley T Paulsen, Brian D Burrell","doi":"10.3389/fnsyn.2022.760330","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.760330","url":null,"abstract":"Endocannabinoids are lipid neuromodulators that are synthesized on demand and primarily signal in a retrograde manner to elicit depression of excitatory and inhibitory synapses. Despite the considerable interest in their potential analgesic effects, there is evidence that endocannabinoids can have both pro-nociceptive and anti-nociceptive effects. The mechanisms contributing to the opposing effects of endocannabinoids in nociception need to be better understood before cannabinoid-based therapies can be effectively utilized to treat pain. Using the medicinal leech, Hirudo verbana, this work investigates whether endocannabinoids modulate tonic inhibition onto non-nociceptive afferents. In voltage clamp recordings, we analyzed changes in the tonic inhibition in pressure-sensitive (P) cells following pre-treatment with endocannabinoids, 2-arachidonoylglycerol (2-AG) or anandamide (AEA). We also tested whether high frequency stimulation (HFS) of nociceptive (N) cells could also modulate tonic inhibition. Both endocannabinoid application and N cell HFS depressed tonic inhibition in the P cell. Depression of tonic inhibition by N cell HFS was blocked by SB 366791 (a TRPV1 inhibitor). SB 366791 also prevented 2-AG-and AEA-induced depression of tonic inhibition. HFS-induced depression was not blocked by tetrahydrolipstatin (THL), which prevents 2-AG synthesis, nor AM 251 (a CB1 receptor inverse agonist). These results illustrate a novel activity-dependent modulation of tonic GABA currents that is mediated by endocannabinoid signaling and is likely to play an important role in sensitization of non-nociceptive afferent pathways.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 ","pages":"760330"},"PeriodicalIF":3.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10550445","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}

引用次数: 3

Complementary Use of Super-Resolution Imaging Modalities to Study the Nanoscale Architecture of Inhibitory Synapses. 互补使用超分辨率成像模式研究抑制突触的纳米结构。

IF 3.7 4区医学

Frontiers in Synaptic Neuroscience Pub Date : 2022-01-01 DOI: 10.3389/fnsyn.2022.852227

Sara E Gookin, Matthew R Taylor, Samantha L Schwartz, Matthew J Kennedy, Mark L Dell'Acqua, Kevin C Crosby, Katharine R Smith

{"title":"Complementary Use of Super-Resolution Imaging Modalities to Study the Nanoscale Architecture of Inhibitory Synapses.","authors":"Sara E Gookin, Matthew R Taylor, Samantha L Schwartz, Matthew J Kennedy, Mark L Dell'Acqua, Kevin C Crosby, Katharine R Smith","doi":"10.3389/fnsyn.2022.852227","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.852227","url":null,"abstract":"The nanoscale architecture of synapses has been investigated using multiple super-resolution methods, revealing a common modular structure for scaffolds, neurotransmitter receptors, and presynaptic proteins. This fundamental organization of proteins into subsynaptic domains (SSDs) is thought to be important for synaptic function and plasticity and common to many types of synapses. Using 3D super-resolution Structured Illumination Microscopy (3D-SIM), we recently showed that GABAergic inhibitory synapses exhibit this nanoscale organizational principle and are composed of SSDs of GABA A receptors (GABA A Rs), the inhibitory scaffold gephyrin, and the presynaptic active zone protein, RIM. Here, we have investigated the use of 3D-SIM and dSTORM to analyze the nanoscale architecture of the inhibitory synaptic adhesion molecule, neuroligin-2 (NL2). NL2 is a crucial mediator of inhibitory synapse formation and organization, associating with both GABA A Rs and gephyrin. However, the nanoscale sub-synaptic distribution NL2 remains unknown. We found that 3D-SIM and dSTORM provide complementary information regarding the distribution of NL2 at the inhibitory synapse, with NL2 forming nanoscale structures that have many similarities to gephyrin nanoscale architecture.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 ","pages":"852227"},"PeriodicalIF":3.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10766603","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}

引用次数: 3