Frontiers in Synaptic Neuroscience最新文献_第10页

High-Resolution Fluorescence Imaging Combined With Computer Simulations to Quantitate Surface Dynamics and Nanoscale Organization of Neuroligin-1 at Synapses. 高分辨率荧光成像结合计算机模拟定量突触表面动力学和神经胶质素-1的纳米级组织

IF 2.8 4区医学

Frontiers in Synaptic Neuroscience Pub Date : 2022-04-25 eCollection Date: 2022-01-01 DOI: 10.3389/fnsyn.2022.835427

Matthieu Lagardère, Adèle Drouet, Matthieu Sainlos, Olivier Thoumine

{"title":"High-Resolution Fluorescence Imaging Combined With Computer Simulations to Quantitate Surface Dynamics and Nanoscale Organization of Neuroligin-1 at Synapses.","authors":"Matthieu Lagardère, Adèle Drouet, Matthieu Sainlos, Olivier Thoumine","doi":"10.3389/fnsyn.2022.835427","DOIUrl":"10.3389/fnsyn.2022.835427","url":null,"abstract":"Neuroligins (NLGNs) form a family of cell adhesion molecules implicated in synapse development, but the mechanisms that retain these proteins at synapses are still incompletely understood. Recent studies indicate that surface-associated NLGN1 is diffusionally trapped at synapses, where it interacts with quasi-static scaffolding elements of the post-synaptic density. Whereas single molecule tracking reveals rapid diffusion and transient immobilization of NLGN1 at synapses within seconds, fluorescence recovery after photobleaching experiments indicate instead a long-term turnover of NLGN1 at synapse, in the hour time range. To gain insight into the mechanisms supporting NLGN1 anchorage at post-synapses and try to reconcile those experimental paradigms, we quantitatively analyzed here live-cell and super-resolution imaging experiments performed on NLGN1 using a newly released simulator of membrane protein dynamics for fluorescence microscopy, FluoSim. Based on a small set of parameters including diffusion coefficients, binding constants, and photophysical rates, the framework describes fairly well the dynamic behavior of extra-synaptic and synaptic NLGN1 over both short and long time ranges, and provides an estimate of NLGN1 copy numbers in post-synaptic densities at steady-state (around 50 dimers). One striking result is that the residence time of NLGN1 at synapses is much longer than what can be expected from extracellular interactions with pre-synaptic neurexins only, suggesting that NLGN1 is stabilized at synapses through multivalent interactions with intracellular post-synaptic scaffolding proteins.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2022-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9083120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44007211","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

cAMP-Dependent Synaptic Plasticity at the Hippocampal Mossy Fiber Terminal 海马苔藓纤维末端camp依赖性突触可塑性

IF 3.7 4区医学

Frontiers in Synaptic Neuroscience Pub Date : 2022-04-04 DOI: 10.3389/fnsyn.2022.861215

Meishar Shahoha, Ronni Cohen, Yoav Ben-Simon, U. Ashery

{"title":"cAMP-Dependent Synaptic Plasticity at the Hippocampal Mossy Fiber Terminal","authors":"Meishar Shahoha, Ronni Cohen, Yoav Ben-Simon, U. Ashery","doi":"10.3389/fnsyn.2022.861215","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.861215","url":null,"abstract":"Cyclic adenosine monophosphate (cAMP) is a crucial second messenger involved in both pre- and postsynaptic plasticity in many neuronal types across species. In the hippocampal mossy fiber (MF) synapse, cAMP mediates presynaptic long-term potentiation and depression. The main cAMP-dependent signaling pathway linked to MF synaptic plasticity acts via the activation of the protein kinase A (PKA) molecular cascade. Accordingly, various downstream putative synaptic PKA target proteins have been linked to cAMP-dependent MF synaptic plasticity, such as synapsin, rabphilin, synaptotagmin-12, RIM1a, tomosyn, and P/Q-type calcium channels. Regulating the expression of some of these proteins alters synaptic release probability and calcium channel clustering, resulting in short- and long-term changes to synaptic efficacy. However, despite decades of research, the exact molecular mechanisms by which cAMP and PKA exert their influences in MF terminals remain largely unknown. Here, we review current knowledge of different cAMP catalysts and potential downstream PKA-dependent molecular cascades, in addition to non-canonical cAMP-dependent but PKA-independent cascades, which might serve as alternative, compensatory or competing pathways to the canonical PKA cascade. Since several other central synapses share a similar form of presynaptic plasticity with the MF, a better description of the molecular mechanisms governing MF plasticity could be key to understanding the relationship between the transcriptional and computational levels across brain regions.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2022-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69623064","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}

引用次数: 5

The Shaping of AMPA Receptor Surface Distribution by Neuronal Activity 神经元活动对AMPA受体表面分布的影响

IF 3.7 4区医学

Frontiers in Synaptic Neuroscience Pub Date : 2022-03-21 DOI: 10.3389/fnsyn.2022.833782

T. Chater, Y. Goda

{"title":"The Shaping of AMPA Receptor Surface Distribution by Neuronal Activity","authors":"T. Chater, Y. Goda","doi":"10.3389/fnsyn.2022.833782","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.833782","url":null,"abstract":"Neurotransmission is critically dependent on the number, position, and composition of receptor proteins on the postsynaptic neuron. Of these, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) are responsible for the majority of postsynaptic depolarization at excitatory mammalian synapses following glutamate release. AMPARs are continually trafficked to and from the cell surface, and once at the surface, AMPARs laterally diffuse in and out of synaptic domains. Moreover, the subcellular distribution of AMPARs is shaped by patterns of activity, as classically demonstrated by the synaptic insertion or removal of AMPARs following the induction of long-term potentiation (LTP) and long-term depression (LTD), respectively. Crucially, there are many subtleties in the regulation of AMPARs, and exactly how local and global synaptic activity drives the trafficking and retention of synaptic AMPARs of different subtypes continues to attract attention. Here we will review how activity can have differential effects on AMPAR distribution and trafficking along with its subunit composition and phosphorylation state, and we highlight some of the controversies and remaining questions. As the AMPAR field is extensive, to say the least, this review will focus primarily on cellular and molecular studies in the hippocampus. We apologise to authors whose work could not be cited directly owing to space limitations.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2022-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42936576","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}

引用次数: 9

Editorial: Activated Synapses 编辑:激活突触

IF 3.7 4区医学

Frontiers in Synaptic Neuroscience Pub Date : 2022-03-18 DOI: 10.3389/fnsyn.2022.875904

F. Rubio, E. Valjent, B. Hope

引用次数: 0

Organization of Presynaptic Autophagy-Related Processes. 突触前自噬相关过程的组织

IF 2.8 4区医学

Frontiers in Synaptic Neuroscience Pub Date : 2022-03-17 eCollection Date: 2022-01-01 DOI: 10.3389/fnsyn.2022.829354

Eckart D Gundelfinger, Anna Karpova, Rainer Pielot, Craig C Garner, Michael R Kreutz

{"title":"Organization of Presynaptic Autophagy-Related Processes.","authors":"Eckart D Gundelfinger, Anna Karpova, Rainer Pielot, Craig C Garner, Michael R Kreutz","doi":"10.3389/fnsyn.2022.829354","DOIUrl":"10.3389/fnsyn.2022.829354","url":null,"abstract":"Brain synapses pose special challenges on the quality control of their protein machineries as they are far away from the neuronal soma, display a high potential for plastic adaptation and have a high energy demand to fulfill their physiological tasks. This applies in particular to the presynaptic part where neurotransmitter is released from synaptic vesicles, which in turn have to be recycled and refilled in a complex membrane trafficking cycle. Pathways to remove outdated and damaged proteins include the ubiquitin-proteasome system acting in the cytoplasm as well as membrane-associated endolysosomal and the autophagy systems. Here we focus on the latter systems and review what is known about the spatial organization of autophagy and endolysomal processes within the presynapse. We provide an inventory of which components of these degradative systems were found to be present in presynaptic boutons and where they might be anchored to the presynaptic apparatus. We identify three presynaptic structures reported to interact with known constituents of membrane-based protein-degradation pathways and therefore may serve as docking stations. These are (i) scaffolding proteins of the cytomatrix at the active zone, such as Bassoon or Clarinet, (ii) the endocytic machinery localized mainly at the peri-active zone, and (iii) synaptic vesicles. Finally, we sketch scenarios, how presynaptic autophagic cargos are tagged and recruited and which cellular mechanisms may govern membrane-associated protein turnover in the presynapse.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2022-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43918349","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

Editorial: Synaptic Diseases: From Biology to Potential Therapy 社论:突触疾病:从生物学到潜在治疗

IF 3.7 4区医学

Frontiers in Synaptic Neuroscience Pub Date : 2022-03-09 DOI: 10.3389/fnsyn.2022.846099

Hansen Wang, R. Balice-Gordon

{"title":"Editorial: Synaptic Diseases: From Biology to Potential Therapy","authors":"Hansen Wang, R. Balice-Gordon","doi":"10.3389/fnsyn.2022.846099","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.846099","url":null,"abstract":"Mutations in genes encoding synaptic or synapse-related proteins that affect the structure and/or function of synapses are responsible for various forms of synaptopathies, including neurodevelopmental, neurodegenerative and psychiatric diseases (Lepeta et al., 2016; Lima Caldeira et al., 2019; Bonnycastle et al., 2021; Germann et al., 2021). Understanding how disease causing genes affect synapse structure and function, and cause circuit and behavioral dysfunction, has been a focus of neuroscience research over several decades. Many challenges remain to be addressed, from identifying rare disease-associated genes, defining the molecular and cellular mechanisms by which the genetic mutations confer disease risk and manifest as phenotypes, understanding how thesemutations affect circuit function, plasticity and behavior, to whether therapeutic interventions can restore function. Studying the pathophysiologic mechanisms underlying synaptopathies will lead to a better understanding of the molecular and cellular mechanisms that govern normal nervous system function, and may eventually help to discover impactful therapeutics (Wang and Doering, 2015; Lepeta et al., 2016; Lima Caldeira et al., 2019; Carroll et al., 2021). This Research Topic has focused on advances in studying common synaptopathies, collecting 31 research and review articles ranging from new insights into fundamental synapse biology to potential therapeutic strategies. Here we summarize each of these articles as a guide to the Research Topic, and highlight the many new research questions stimulated by the work.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2022-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47757253","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}

引用次数: 0

The Synaptic Extracellular Matrix: Long-Lived, Stable, and Still Remarkably Dynamic 突触细胞外基质：长寿、稳定且仍具有显著的动态性

IF 3.7 4区医学

Frontiers in Synaptic Neuroscience Pub Date : 2022-03-08 DOI: 10.3389/fnsyn.2022.854956

T. Dankovich, S. Rizzoli

引用次数: 15

Multiple Roles of Actin in Exo- and Endocytosis. 肌动蛋白在外吞和内吞过程中的多重作用

IF 2.8 4区医学

Frontiers in Synaptic Neuroscience Pub Date : 2022-03-04 eCollection Date: 2022-01-01 DOI: 10.3389/fnsyn.2022.841704

Ling-Gang Wu, Chung Yu Chan

{"title":"Multiple Roles of Actin in Exo- and Endocytosis.","authors":"Ling-Gang Wu, Chung Yu Chan","doi":"10.3389/fnsyn.2022.841704","DOIUrl":"10.3389/fnsyn.2022.841704","url":null,"abstract":"Cytoskeletal filamentous actin (F-actin) has long been considered a molecule that may regulate exo- and endocytosis. However, its exact roles remained elusive. Recent studies shed new light on many crucial roles of F-actin in regulating exo- and endocytosis. Here, this progress is reviewed from studies of secretory cells, particularly neurons and endocrine cells. These studies reveal that F-actin is involved in mediating all kinetically distinguishable forms of endocytosis, including ultrafast, fast, slow, bulk, and overshoot endocytosis, likely via membrane pit formation. F-actin promotes vesicle replenishment to the readily releasable pool most likely via active zone clearance, which may sustain synaptic transmission and overcome short-term depression of synaptic transmission during repetitive firing. By enhancing plasma membrane tension, F-actin promotes fusion pore expansion, vesicular content release, and a fusion mode called shrink fusion involving fusing vesicle shrinking. Not only F-actin, but also the F-actin assembly pathway, including ATP hydrolysis, N-WASH, and formin, are involved in mediating these roles of exo- and endocytosis. Neurological disorders, including spinocerebellar ataxia 13 caused by Kv3.3 channel mutation, may involve impairment of F-actin and its assembly pathway, leading in turn to impairment of exo- and endocytosis at synapses that may contribute to neurological disorders.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2022-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8931529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40308176","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

Hearing Loss Increases Inhibitory Effects of Prefrontal Cortex Stimulation on Sound Evoked Activity in Medial Geniculate Nucleus. 听力损失增加前额皮质刺激对内侧膝状核声诱发活动的抑制作用

IF 2.8 4区医学

Frontiers in Synaptic Neuroscience Pub Date : 2022-03-01 eCollection Date: 2022-01-01 DOI: 10.3389/fnsyn.2022.840368

Chenae De Vis, Kristin M Barry, Wilhelmina H A M Mulders

{"title":"Hearing Loss Increases Inhibitory Effects of Prefrontal Cortex Stimulation on Sound Evoked Activity in Medial Geniculate Nucleus.","authors":"Chenae De Vis, Kristin M Barry, Wilhelmina H A M Mulders","doi":"10.3389/fnsyn.2022.840368","DOIUrl":"10.3389/fnsyn.2022.840368","url":null,"abstract":"Sensory gating is the process whereby irrelevant sensory stimuli are inhibited on their way to higher cortical areas, allowing for focus on salient information. Sensory gating circuitry includes the thalamus as well as several cortical regions including the prefrontal cortex (PFC). Defective sensory gating has been implicated in a range of neurological disorders, including tinnitus, a phantom auditory perception strongly associated with cochlear trauma. Recently, we have shown in rats that functional connectivity between PFC and auditory thalamus, i.e., the medial geniculate nucleus (MGN), changes following cochlear trauma, showing an increased inhibitory effect from PFC activation on the spontaneous firing rate of MGN neurons. In this study, we further investigated this phenomenon using a guinea pig model, in order to demonstrate the validity of our finding beyond a single species and extend data to include data on sound evoked responses. Effects of PFC electrical stimulation on spontaneous and sound-evoked activity of single neurons in MGN were recorded in anaesthetised guinea pigs with normal hearing or hearing loss 2 weeks after acoustic trauma. No effect, inhibition and excitation were observed following PFC stimulation. The proportions of these effects were not different in animals with normal hearing and hearing loss but the magnitude of effect was. Indeed, hearing loss significantly increased the magnitude of inhibition for sound evoked responses, but not for spontaneous activity. The findings support previous observations that PFC can modulate MGN activity and that functional changes occur within this pathway after cochlear trauma. These data suggest hearing loss can alter sensory gating which may be a contributing factor toward tinnitus development.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8921694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46734421","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

Synaptic Vesicle Recycling and the Endolysosomal System: A Reappraisal of Form and Function 突触囊泡循环和内溶酶体系统:形式和功能的重新评价

IF 3.7 4区医学

Frontiers in Synaptic Neuroscience Pub Date : 2022-02-25 DOI: 10.3389/fnsyn.2022.826098

D. Ivanova, M. Cousin

{"title":"Synaptic Vesicle Recycling and the Endolysosomal System: A Reappraisal of Form and Function","authors":"D. Ivanova, M. Cousin","doi":"10.3389/fnsyn.2022.826098","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.826098","url":null,"abstract":"The endolysosomal system is present in all cell types. Within these cells, it performs a series of essential roles, such as trafficking and sorting of membrane cargo, intracellular signaling, control of metabolism and degradation. A specific compartment within central neurons, called the presynapse, mediates inter-neuronal communication via the fusion of neurotransmitter-containing synaptic vesicles (SVs). The localized recycling of SVs and their organization into functional pools is widely assumed to be a discrete mechanism, that only intersects with the endolysosomal system at specific points. However, evidence is emerging that molecules essential for endolysosomal function also have key roles within the SV life cycle, suggesting that they form a continuum rather than being isolated processes. In this review, we summarize the evidence for key endolysosomal molecules in SV recycling and propose an alternative model for membrane trafficking at the presynapse. This includes the hypotheses that endolysosomal intermediates represent specific functional SV pools, that sorting of cargo to SVs is mediated via the endolysosomal system and that manipulation of this process can result in both plastic changes to neurotransmitter release and pathophysiology via neurodegeneration.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2022-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45104694","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}

引用次数: 10