Frontiers in Synaptic Neuroscience最新文献

{"title":"Vagally-mediated heart block after myocardial infarction associated with plasticity of epicardial neurons controlling the atrioventricular node.","authors":"John D Tompkins,&nbsp;Una Buckley,&nbsp;Siamak Salavatian,&nbsp;Kalyanam Shivkumar,&nbsp;Jeffrey L Ardell","doi":"10.3389/fnsyn.2022.960458","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.960458","url":null,"abstract":"<p><p>Imbalances in the opposing actions of sympathetic and parasympathetic nerves controlling the heart enhance risk for arrhythmia and sudden cardiac death after myocardial infarction (MI). Plasticity in peripheral neuron function may underlie the observed changes in cardiomotor nerve activity. We studied vagal control of the heart in pigs after chronic infarction of the left ventricle. Stimulation of the cervical vagus nerve produced greater bradycardic responses 8-weeks after MI. Recordings of epicardial electrocardiograms demonstrate increased severity and duration of atrioventricular (AV) block in MI-pigs during 20 Hz vagal stimulation. Intracellular voltage recordings from isolated neurons of the inferior vena cava-inferior left atrium (IVC-ILA) ganglionated plexus, a cluster of epicardial neurons receiving innervation from the vagus known to regulate the AV node, were used to assess plasticity of membrane and synaptic physiology of intrinsic cardiac neurons (ICNs) after MI. Changes to both passive and active membrane properties were observed, including more negative resting membrane potentials and greater input resistances in MI-pig ICNs, concomitant with a depression of neuronal excitability. Immunoreactivity to pituitary adenylate cyclase-activating polypeptide (PACAP), a cardiotropic peptide known to modulate cardiac neuron excitability, was localized to perineuronal varicosities surrounding pig IVC-ILA neurons. Exogenous application of PACAP increased excitability of control but not MI-ICNs. Stimulation (20 Hz) of interganglionic nerves in the <i>ex vivo</i> whole-mount preparations elicited slow excitatory postsynaptic potentials (sEPSPs) which persisted in hexamethonium (500 μM), but were blocked by atropine (1 μM), indicating muscarinic receptor-mediated inhibition of M-current. Extracellular application of 1 mM BaCl₂ to inhibit M-current increased neuronal excitability. The muscarine-sensitive sEPSPs were observed more frequently and were of larger amplitude in IVC-ILA neurons from MI animals. In conclusion, we suggest the increased probability of muscarinic sEPSPs play a role in the potentiation of the vagus nerve mediated-slowing of AV nodal conduction following chronic MI. We identify both a novel role of a muscarinic sensitive current in the regulation of synaptic strength at ICNs projecting to the AV node, and demonstrate changes to both intrinsic plasticity and synaptic plasticity of IVC-ILA neurons which may contribute to greater risk for heart block and sudden cardiac death after MI.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":"960458"},"PeriodicalIF":3.7,"publicationDate":"2022-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9488518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33478816","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":"Synaptic spinules are reliable indicators of excitatory presynaptic bouton size and strength and are ubiquitous components of excitatory synapses in CA1 hippocampus.","authors":"Ashley Gore,&nbsp;Amaliya Yurina,&nbsp;Anastasia Yukevich-Mussomeli,&nbsp;Marc Nahmani","doi":"10.3389/fnsyn.2022.968404","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.968404","url":null,"abstract":"<p><p>Synaptic spinules are thin, finger-like projections from one neuron that become embedded within the presynaptic or postsynaptic compartments of another neuron. While spinules are conserved features of synapses across the animal kingdom, their specific function(s) remain unknown. Recent focused ion beam scanning electron microscopy (FIB-SEM) image volume analyses have demonstrated that spinules are embedded within ∼25% of excitatory boutons in primary visual cortex, yet the diversity of spinule sizes, origins, and ultrastructural relationships to their boutons remained unclear. To begin to uncover the function of synaptic spinules, we sought to determine the abundance, origins, and 3D ultrastructure of spinules within excitatory presynaptic spinule-bearing boutons (SBBs) in mammalian CA1 hippocampus and compare them with presynaptic boutons bereft of spinules (non-SBBs). Accordingly, we performed a comprehensive 3D analysis of every excitatory presynaptic bouton, their embedded spinules, and postsynaptic densities, within a 5 nm isotropic FIB-SEM image volume from CA1 hippocampus of an adult male rat. Surprisingly, we found that ∼74% of excitatory presynaptic boutons in this volume contained at least one spinule, suggesting they are fundamental components of excitatory synapses in CA1. In addition, we found that SBBs are 2.5-times larger and have 60% larger postsynaptic densities (PSDs) than non-SBBs. Moreover, synaptic spinules within SBBs are clearly differentiated into two groups: small clathrin-coated spinules, and 29-times larger spinules without clathrin. Together, these findings suggest that the presence of a spinule is a marker for stronger and more stable presynaptic boutons in CA1, and that synaptic spinules serve at least two separable and distinct functions.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":"968404"},"PeriodicalIF":3.7,"publicationDate":"2022-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9403541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33441916","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":"Assessment of cardiac function in rat endovascular perforation model of subarachnoid hemorrhage; A model of subarachnoid hemorrhage-induced cardiac dysfunction.","authors":"Masahito Munakata,&nbsp;Hideaki Kanazawa,&nbsp;Kensuke Kimura,&nbsp;Takahide Arai,&nbsp;Hiroaki Sukegawa,&nbsp;Keiichi Fukuda","doi":"10.3389/fnsyn.2022.919998","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.919998","url":null,"abstract":"<p><p>Although the association between cardiac dysfunction and subarachnoid hemorrhage (SAH) has been recognized, its precise underlying mechanism remains unknown. Furthermore, no suitable animal models are available to study this association. Here, we established an appropriate animal model of SAH-induced cardiac dysfunction and elucidated its mechanism. In this rat model, contrast-enhanced computed tomography of the brain confirmed successful induction of SAH. Electrocardiography detected abnormalities in 55% of the experimental animals, while echocardiography indicated cardiac dysfunction in 30% of them. Further evaluation of left ventriculography confirmed cardiac dysfunction, which was transient and recovered over time. Additionally, in this SAH model, the expression of the acute phase reaction protein, proto-oncogene c-Fos increased in the paraventricular hypothalamic nucleus (PVN), the sympathetic nerve center of the brain. Polymerase chain reaction analysis revealed that the SAH model with cardiac dysfunction had higher levels of the macrophage-associated chemokine (C-X-C motif) ligand 1 (CXCL-1) and chemokine (C-C motif) ligand 2 (CCL-2) than the SAH model without cardiac dysfunction. Our results suggested that SAH caused inflammation and macrophage activation in the PVN, leading to sympathetic hyperexcitability that might cause cardiac dysfunction directly and indirectly. This animal model may represent a powerful tool to investigate the mechanisms of the brain-heart pathway.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":"919998"},"PeriodicalIF":3.7,"publicationDate":"2022-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9396209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33437879","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":"Healthy cardiac myocytes can decrease sympathetic hyperexcitability in the early stages of hypertension.","authors":"Harvey Davis, Kun Liu, Ni Li, Dan Li, David J Paterson","doi":"10.3389/fnsyn.2022.949150","DOIUrl":"10.3389/fnsyn.2022.949150","url":null,"abstract":"<p><p>Sympathetic neurons are powerful drivers of cardiac excitability. In the early stages of hypertension, sympathetic hyperactivity is underpinned by down regulation of M current and increased activity of Cav_2.2 that is associated with greater intracellular calcium transients and enhanced neurotransmission. Emerging evidence suggests that retrograde signaling from the myocyte itself can modulate synaptic plasticity. Here we tested the hypothesis that cross culturing healthy myocytes onto diseased stellate neurons could influence sympathetic excitability. We employed neuronal mono-cultures, co-cultures of neonatal ventricular myocytes and sympathetic stellate neurons, and mono-cultures of sympathetic neurons with media conditioned by myocytes from normal (Wistar) and pre-hypertensive (SHR) rats, which have heightened sympathetic responsiveness. Neuronal firing properties were measured by current-clamp as a proxy for neuronal excitability. SHR neurons had a maximum higher firing rate, and reduced rheobase compared to Wistar neurons. There was no difference in firing rate or other biophysical properties in Wistar neurons when they were co-cultured with healthy myocytes. However, the firing rate decreased, phenocopying the Wistar response when either healthy myocytes or media in which healthy myocytes were grown was cross-cultured with SHR neurons. This supports the idea of a paracrine signaling pathway from the healthy myocyte to the diseased neuron, which can act as a modulator of sympathetic excitability.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 ","pages":"949150"},"PeriodicalIF":2.8,"publicationDate":"2022-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9386373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9163176","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":"rTg(Tau_P301L)4510 mice exhibit increased VGlut1 in hippocampal presynaptic glutamatergic vesicles and increased extracellular glutamate release.","authors":"Erika Taipala,&nbsp;Jeremiah C Pfitzer,&nbsp;Morgan Hellums,&nbsp;Miranda N Reed,&nbsp;Michael W Gramlich","doi":"10.3389/fnsyn.2022.925546","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.925546","url":null,"abstract":"<p><p>The molecular pathways that contribute to the onset of symptoms in tauopathy models, including Alzheimer's disease (AD), are difficult to distinguish because multiple changes can happen simultaneously at different stages of disease progression. Understanding early synaptic alterations and their supporting molecular pathways is essential to develop better pharmacological targets to treat AD. Here, we focus on an early onset rTg(Tau_P301<i>L</i> )4510 tauopathy mouse model that exhibits hyperexcitability in hippocampal neurons of adult mice that is correlated with presynaptic changes and increased extracellular glutamate levels. However, it is not clear if increased extracellular glutamate is caused by presynaptic changes alone, or if presynaptic changes are a contributing factor among other factors. To determine whether pathogenic tau alters presynaptic function and glutamate release, we studied cultured hippocampal neurons at 14-18 days <i>in vitro</i> (DIV) from animals of both sexes to measure presynaptic changes in tau_P301L positive mice. We observed that presynaptic vesicles exhibit increased vesicular glutamate transporter 1 (VGlut1) using immunohistochemistry of fixed cells and an established pH-sensitive green fluorescent protein approach. We show that tau_P301L positive neurons exhibit a 40% increase in VGlut1 per vesicle compared to tau_P301L negative littermates. Further, we use the extracellular glutamate reporter iGluSnFR to show that increased VGlut1 per vesicle directly translates into a 40% increase in extracellular glutamate. Together, these results show that increased extracellular glutamate levels observed in tau_P301L mice are not caused by increased vesicle exocytosis probability but rather are directly related to increased VGlut1 transporters per synaptic vesicle.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":"925546"},"PeriodicalIF":3.7,"publicationDate":"2022-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9383415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40713294","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":"Glucagon-like peptide 1 and glucose-dependent insulinotropic peptide hormones and novel receptor agonists protect synapses in Alzheimer's and Parkinson's diseases.","authors":"Christian Hölscher","doi":"10.3389/fnsyn.2022.955258","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.955258","url":null,"abstract":"<p><p>Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are peptide hormones and growth factors. A major pathological feature of both Alzheimer's dis-ease (AD) and Parkinson's disease (PD) is the loss of synaptic transmission in the cortex in AD and the loss of dopaminergic synapses in the nigra-striatal dopaminergic projection. Several studies demonstrate that GLP-1 and GIP receptor agonists protect synapses and synaptic transmission from the toxic events that underlie AD and PD. In a range of AD animal models, treatment with GLP-1, GIP, or dual-GLP-1/GIP receptor agonists effectively protected cognition, synaptic trans-mission, long-term potentiation (LTP), and prevented the loss of synapses and neurons. In PD models, dopaminergic production resumed and synapses became functional again. Importantly, the GLP-1 receptor agonists exendin-4 and liraglutide have shown good protective effects in clinical trials in AD and PD patients. Studies show that growth factors and peptide drugs that can cross the blood-brain barrier (BBB) better are more potent than those that do not cross the BBB. We therefore developed dual-GLP-1/GIP receptor agonists that can cross the BBB at an enhanced rate and showed superior protective properties on synapses in animal models of AD and PD.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":"955258"},"PeriodicalIF":3.7,"publicationDate":"2022-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9363704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40696435","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":"Editorial: Regulation of AMPA Receptors, From the Genetic to the Functional Level.","authors":"Alberto Ouro,&nbsp;Tak Pan Wong,&nbsp;Laura Jiménez-Sánchez","doi":"10.3389/fnsyn.2022.952564","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.952564","url":null,"abstract":"the central and peripheral systems. They are in postsynaptic cells, but can also be found in pre-synaptic sites and glia processes. glutamate the postsynaptic AMPARs mediate the fast excitatory synaptic transmission which can be changed in an activity dependent manner and involve a minority of Ca 2 + permeable AMPARs. This Research Topic describes several new mechanisms that regulate AMPAR trafficking and plasticity;","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":"952564"},"PeriodicalIF":3.7,"publicationDate":"2022-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40556119","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":"Corrigendum: Editorial: Activated Synapses.","authors":"F Javier Rubio,&nbsp;Emmanuel Valjent,&nbsp;Bruce T Hope","doi":"10.3389/fnsyn.2022.932503","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.932503","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fnsyn.2022.875904.].</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":"932503"},"PeriodicalIF":3.7,"publicationDate":"2022-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40580741","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":"Astrocyte: A Foe or a Friend in Intellectual Disability-Related Diseases.","authors":"Busong Wang,&nbsp;Lu Zou,&nbsp;Min Li,&nbsp;Liang Zhou","doi":"10.3389/fnsyn.2022.877928","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.877928","url":null,"abstract":"<p><p>Intellectual disabilities are a type of neurodevelopmental disease caused by neurological dysfunction. Their incidence is largely associated with neural development. Astrocytes are the most widely distributed cells in the mammalian brain. Previous studies have reported that astrocytes only supported and separated the neurons in the brain. However, recent studies have found that they also play an important role in neural development. Understanding the astrocyte mechanism in intellectual development disorder-related diseases will help provide new therapeutic targets for the treatment of intellectual disability-related diseases. This mini-review introduced the association between astrocyte and intellectual disabilities. Furthermore, recent advances in genetic and environmental factors causing intellectual disability and different pharmaceutical effects of intellectual disability-related drugs on astrocytes have been summarised. Finally, we discussed future perspectives of astrocyte-based therapy for intellectual disability.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":"877928"},"PeriodicalIF":3.7,"publicationDate":"2022-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40603771","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":"Regulation of Inhibitory Signaling at the Receptor and Cellular Level; Advances in Our Understanding of GABAergic Neurotransmission and the Mechanisms by Which It Is Disrupted in Epilepsy.","authors":"Allison E Tipton,&nbsp;Shelley J Russek","doi":"10.3389/fnsyn.2022.914374","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.914374","url":null,"abstract":"<p><p>Inhibitory signaling in the brain organizes the neural circuits that orchestrate how living creatures interact with the world around them and how they build representations of objects and ideas. Without tight control at multiple points of cellular engagement, the brain's inhibitory systems would run down and the ability to extract meaningful information from excitatory events would be lost leaving behind a system vulnerable to seizures and to cognitive decline. In this review, we will cover many of the salient features that have emerged regarding the dynamic regulation of inhibitory signaling seen through the lens of cell biology with an emphasis on the major building blocks, the ligand-gated ion channel receptors that are the first transduction point when the neurotransmitter GABA is released into the synapse. Epilepsy association will be used to indicate importance of key proteins and their pathways to brain function and to introduce novel areas for therapeutic intervention.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":"914374"},"PeriodicalIF":3.7,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40645333","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}