Frontiers in Synaptic Neuroscience最新文献

{"title":"Cyclic AMP response element-binding protein (CREB) transcription factor in astrocytic synaptic communication.","authors":"Jooyoung Kim,&nbsp;Bong-Kiun Kaang","doi":"10.3389/fnsyn.2022.1059918","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.1059918","url":null,"abstract":"<p><p>Astrocytes are known to actively participate in synaptic communication by forming structures called tripartite synapses. These synapses consist of presynaptic axon terminals, postsynaptic dendritic spines, and astrocytic processes where astrocytes release and receive transmitters. Although the transcription factor cyclic AMP response element (CRE)-binding protein (CREB) has been actively studied as an important factor for mediating synaptic activity-induced responses in neurons, its role in astrocytes is relatively unknown. Synaptic signals are known to activate various downstream pathways in astrocytes, which can activate the CREB transcription factor. Therefore, there is a need to summarize studies on astrocytic intracellular pathways that are induced by synaptic communication resulting in activation of the CREB pathway. In this review, we discuss the various neurotransmitter receptors and intracellular pathways that can induce CREB activation and CREB-induced gene regulation in astrocytes.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 ","pages":"1059918"},"PeriodicalIF":3.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9845270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10636122","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":"Dentate Granule Cells Are Hyperexcitable in the TgF344-AD Rat Model of Alzheimer's Disease.","authors":"Lindsey A Smith,&nbsp;Anthoni M Goodman,&nbsp;Lori L McMahon","doi":"10.3389/fnsyn.2022.826601","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.826601","url":null,"abstract":"<p><p>The dentate gyrus is both a critical gatekeeper for hippocampal signal processing and one of the first brain regions to become dysfunctional in Alzheimer's disease (AD). Accordingly, the appropriate balance of excitation and inhibition through the dentate is a compelling target for mechanistic investigation and therapeutic intervention in early AD. Previously, we reported an increased long-term potentiation (LTP) magnitude at medial perforant path-dentate granule cell (MPP-DGC) synapses in slices from both male and acutely ovariectomized female TgF344-AD rats compared with wild type (Wt) as early as 6 months of age that is accompanied by an increase in steady-state postsynaptic depolarization during the high-frequency stimulation used to induce plasticity. Subsequently, we found that heightened function of β-adrenergic receptors (β-ARs) drives the increase in the LTP magnitude, but the increase in steady-state depolarization was only partially due to β-AR activation. As we previously reported no detectable difference in spine density or presynaptic release probability, we entertained the possibility that DGCs themselves might have modified passive or active membrane properties, which may contribute to the significant increase in charge transfer during high-frequency stimulation. Using brain slice electrophysiology from 6-month-old female rats acutely ovariectomized to eliminate variability due to fluctuating plasma estradiol, we found significant changes in passive membrane properties and active membrane properties leading to increased DGC excitability in TgF344-AD rats. Specifically, TgF344-AD DGCs have an increased input resistance and decreased rheobase, decreased sag, and increased action potential (AP) spike accommodation. Importantly, we found that for the same amount of depolarizing current injection, DGCs from TgF344-AD compared with Wt rats have a larger magnitude voltage response, which was accompanied by a decreased delay to fire the first action potential, indicating TgF344-AD DGCs membranes are more excitable. Taken together, DGCs in TgF344-AD rats are more excitable, which likely contributes to the heightened depolarization during high-frequency synaptic activation.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 ","pages":"826601"},"PeriodicalIF":3.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9267382","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":"Identification of Synaptic DGKθ Interactors That Stimulate DGKθ Activity.","authors":"Casey N Barber,&nbsp;Hana L Goldschmidt,&nbsp;Qianqian Ma,&nbsp;Lauren R Devine,&nbsp;Robert N Cole,&nbsp;Richard L Huganir,&nbsp;Daniel M Raben","doi":"10.3389/fnsyn.2022.855673","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.855673","url":null,"abstract":"<p><p>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.</p>","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}

{"title":"Diverse organization of voltage-gated calcium channels at presynaptic active zones.","authors":"Weijia Zhang,&nbsp;He-Hai Jiang,&nbsp;Fujun Luo","doi":"10.3389/fnsyn.2022.1023256","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.1023256","url":null,"abstract":"<p><p>Synapses are highly organized but are also highly diverse in their organization and properties to allow for optimizing the computing power of brain circuits. Along these lines, voltage-gated calcium (CaV) channels at the presynaptic active zone are heterogeneously organized, which creates a variety of calcium dynamics profiles that can shape neurotransmitter release properties of individual synapses. Extensive studies have revealed striking diversity in the subtype, number, and distribution of CaV channels, as well as the nanoscale topographic relationships to docked synaptic vesicles. Further, multi-protein complexes including RIMs, RIM-binding proteins, CAST/ELKS, and neurexins are required for coordinating the diverse organization of CaV channels at the presynaptic active zone. In this review, we highlight major advances in the studies of the functional organization of presynaptic CaV channels and discuss their physiological implications for synaptic transmission and short-term plasticity.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 ","pages":"1023256"},"PeriodicalIF":3.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9760684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10411137","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":"A review of the mechanisms underlying the role of the <i>GIPC3</i> gene in hereditary deafness.","authors":"Xinxin Li,&nbsp;Lin Shi,&nbsp;Liang Wang","doi":"10.3389/fnsyn.2022.1101587","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.1101587","url":null,"abstract":"<p><p>The GAIP interacting protein c terminus (<i>GIPC</i>) genes encode a small family of proteins characterized by centrally located PDZ domains. <i>GIPC3</i> encodes a 312 amino acid protein. Variants of human <i>GIPC3</i> are associated with non-syndromic hearing loss. <i>GIPC3</i> is one of over a hundred different genes with variants causing human deafness. Screening for variants of <i>GIPC3</i> is essential for early detection of hearing loss in children and eventually treatment of deafness. Accordingly, this paper assesses the status of research developments on the role of <i>GIPC3</i> in hereditary deafness and the effects of pathogenic variants on the auditory system.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 ","pages":"1101587"},"PeriodicalIF":3.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9872657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10625587","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":"Protein phosphatase-1 inhibitor-2 promotes PP1<i>γ</i> positive regulation of synaptic transmission.","authors":"Karl Foley,&nbsp;Haider Altimimi,&nbsp;Hailong Hou,&nbsp;Yu Zhang,&nbsp;Cody McKee,&nbsp;Makaía M Papasergi-Scott,&nbsp;Hongtian Yang,&nbsp;Abigail Mayer,&nbsp;Nancy Ward,&nbsp;David M MacLean,&nbsp;Angus C Nairn,&nbsp;David Stellwagen,&nbsp;Houhui Xia","doi":"10.3389/fnsyn.2022.1021832","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.1021832","url":null,"abstract":"<p><p>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 <i>in vitro</i>, our previous work has elucidated that, <i>in vivo</i>, I-2 may act as a positive regulator of PP1. Here we show that I-2 and PP1<i>γ</i>, but not PP1α, positively regulate synaptic transmission in hippocampal neurons. Moreover, we demonstrated that I-2 enhanced PP1<i>γ</i> 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 <i>in vivo</i> 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.</p>","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}

{"title":"Segregation of D1 and D2 dopamine receptors in the striatal direct and indirect pathways: An historical perspective.","authors":"Charles R Gerfen","doi":"10.3389/fnsyn.2022.1002960","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.1002960","url":null,"abstract":"<p><p>The direct and indirect striatal pathways form a cornerstone of the circuits of the basal ganglia. Dopamine has opponent affects on the function of these pathways due to the segregation of the D1- and D2-dopamine receptors in the spiny projection neurons giving rise to the direct and indirect pathways. An historical perspective is provided on the discovery of dopamine receptor segregation leading to models of how the direct and indirect affect motor behavior.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 ","pages":"1002960"},"PeriodicalIF":3.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9892636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10666409","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":"The biological alterations of synapse/synapse formation in sepsis-associated encephalopathy.","authors":"Chuan Tang,&nbsp;Ye Jin,&nbsp;Huan Wang","doi":"10.3389/fnsyn.2022.1054605","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.1054605","url":null,"abstract":"<p><p>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.</p>","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}

{"title":"Unraveling Functional Diversity of Cortical Synaptic Architecture Through the Lens of Population Coding.","authors":"Jacob L Yates,&nbsp;Benjamin Scholl","doi":"10.3389/fnsyn.2022.888214","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.888214","url":null,"abstract":"<p><p>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 <i>in vivo</i> 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 <i>in vivo</i>. 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 <i>in vivo</i> 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.</p>","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}

{"title":"Activity-Dependent Modulation of Tonic GABA Currents by Endocannabinoids in <i>Hirudo verbana</i>.","authors":"Riley T Paulsen,&nbsp;Brian D Burrell","doi":"10.3389/fnsyn.2022.760330","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.760330","url":null,"abstract":"<p><p>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, <i>Hirudo verbana</i>, 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.</p>","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}