Frontiers in Synaptic Neuroscience最新文献

{"title":"A novel peptide inhibitor of TRPM2 channels improves recovery of memory function following traumatic brain injury.","authors":"James E Orfila, Robert M Dietz, Christian Schroeder, Olivia P Patsos, Amelia Burch, Kiara E Bahamonde, Kelley A Coakley, Danelle J Carter, Amy C Clevenger, Tara B Hendry-Hofer, Tuan D Le, Joseph K Maddry, Steven G Schauer, Vikhyat S Bebarta, Paco S Herson","doi":"10.3389/fnsyn.2025.1534379","DOIUrl":"https://doi.org/10.3389/fnsyn.2025.1534379","url":null,"abstract":"<p><p>Traumatic Brain Injury (TBI) is a leading cause of mortality and morbidity in adults and can lead to long-term disability, including cognitive and motor deficits. Despite advances in research, there are currently no pharmacological interventions to improve outcomes after TBI. Studies suggest that non-selective transient receptor potential melastatin 2 (TRPM2) channels contribute to brain injury in models of ischemia, however TRPM2 remains understudied following TBI. Thus, we utilized TRPM2 KO mice and a novel TRPM2 inhibiting peptide, tatM2NX, to assess the role of TRPM2 in TBI-induced injury and functional recovery. This study used histological analysis of injury, neurobehavior and electrophysiology to assess the role of TRPM2 on injury and cognitive recovery (memory) impairments using the controlled cortical impact (CCI) model to induce TBI in mice. Histological analysis used to investigate brain injury volume at 7 days after TBI showed sex differences in response to injury in TRPM2 KO mice but no pharmacological effects in our WT mice. A contextual fear-conditioning task was used to study memory function 7 or 30 days after TBI and demonstrates that sham-operated mice exhibited significant freezing behavior compared to TBI-operated mice, indicating impaired memory function. Mice administered tat-M2NX 2 h after TBI exhibited a significant reduction of freezing behavior compared to control tat-scrambled (tat-SCR)-treated mice, suggesting improvement in memory function after TBI. To test the effect of TBI on hippocampal long-term potentiation (LTP), a well-established cellular model of synaptic plasticity associated with changes in learning and memory, extracellular field recordings of CA1 neurons were performed in hippocampal slices prepared 7 days after TBI. Consistent with our behavioral testing, we observed impaired hippocampal LTP in mice following TBI (tat-SCR), compared to sham control mice. However, mice treated with tat-M2NX after TBI exhibited preserved LTP, consistent with the improved memory function observed in our behavioral studies. While this data implicates TRPM2 in brain pathology following TBI, the improvement in memory function without providing histological protection suggests that administration of tatM2NX at an acute time point differentially affects hippocampal regions compared to cortical regions.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"17 ","pages":"1534379"},"PeriodicalIF":2.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003500","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":"High frequency stimulation activates hot spots of spontaneous synaptic transmission.","authors":"Herson Astacio, Maria Bykhovskaia","doi":"10.3389/fnsyn.2025.1539868","DOIUrl":"https://doi.org/10.3389/fnsyn.2025.1539868","url":null,"abstract":"<p><p>Neuronal transmitters are released at the morphological specializations known as active zones (AZs). Transmitters can be released either in response to a stimulus or spontaneously, and spontaneous transmission is a vital component of neuronal communication. Employing postsynaptically tethered calcium sensor GCaMP, we investigated how nerve stimulation affects spontaneous transmission at individual AZs at the <i>Drosophila</i> neuromuscular synapse. Optical monitoring of spontaneous transmission at individual AZs revealed that prolonged high-frequency stimulation (HFS, 30 Hz for 1 min) selectively activates the hot spots of spontaneous transmission, including the individual AZs with elevated activities as well as AZ clusters. In contrast, a brief tetanus (2 s) activated numerous low-activity AZs. We employed Monte-Carlo simulations of spontaneous transmission based on a three-state model of AZ preparedness, which incorporated longer-lasting (minutes) and shorter-lasting (sub-seconds to seconds) high-activity states of AZs. The simulations produced an accurate quantitative description of the variability and time-course of spontaneous transmission at individual AZs before and after the stimulation and suggested that HFS activates both longer-lasting and shorter-lasting states of AZ preparedness.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"17 ","pages":"1539868"},"PeriodicalIF":2.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987570","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 spatial model of autophosphorylation of CaMKII predicts that the lifetime of phospho-CaMKII after induction of synaptic plasticity is greatly prolonged by CaM-trapping.","authors":"Thomas M Bartol, Mariam Ordyan, Terrence J Sejnowski, Padmini Rangamani, Mary B Kennedy","doi":"10.3389/fnsyn.2025.1547948","DOIUrl":"https://doi.org/10.3389/fnsyn.2025.1547948","url":null,"abstract":"<p><p>Long-term potentiation (LTP) is a biochemical process that underlies learning in excitatory glutamatergic synapses in the Central Nervous System (CNS). A critical early driver of LTP is autophosphorylation of the abundant postsynaptic enzyme, Ca²⁺/calmodulin-dependent protein kinase II (CaMKII). Autophosphorylation is initiated by Ca²⁺ flowing through NMDA receptors activated by strong synaptic activity. Its lifetime is ultimately determined by the balance of the rates of autophosphorylation and of dephosphorylation by protein phosphatase 1 (PP1). Here we have modeled the autophosphorylation and dephosphorylation of CaMKII during synaptic activity in a spine synapse using MCell4, an open source computer program for creating particle-based stochastic, and spatially realistic models of cellular microchemistry. The model integrates four earlier detailed models of separate aspects of regulation of spine Ca²⁺ and CaMKII activity, each of which incorporate experimentally measured biochemical parameters and have been validated against experimental data. We validate the composite model by showing that it accurately predicts previous experimental measurements of effects of NMDA receptor activation, including high sensitivity of induction of LTP to phosphatase activity <i>in vivo,</i> and persistence of autophosphorylation for a period of minutes after the end of synaptic stimulation. We then use the model to probe aspects of the mechanism of regulation of autophosphorylation of CaMKII that are difficult to measure <i>in vivo</i>. We examine the effects of \"CaM-trapping,\" a process in which the affinity for Ca²⁺/CaM increases several hundred-fold after autophosphorylation. We find that CaM-trapping does not increase the proportion of autophosphorylated subunits in holoenzymes after a complex stimulus, as previously hypothesized. Instead, CaM-trapping may dramatically prolong the lifetime of autophosphorylated CaMKII through steric hindrance of dephosphorylation by protein phosphatase 1. The results provide motivation for experimental measurement of the extent of suppression of dephosphorylation of CaMKII by bound Ca²⁺/CaM. The composite MCell4 model of biochemical effects of complex stimuli in synaptic spines is a powerful new tool for realistic, detailed dissection of mechanisms of synaptic plasticity.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"17 ","pages":"1547948"},"PeriodicalIF":2.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976038","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":"Postsynaptic spiking determines anti-Hebbian LTD in visual cortex basket cells.","authors":"Christina Y C Chou, Wouter J Droogers, Txomin Lalanne, Eric Fineberg, Tal Klimenko, Hannah Owens, P Jesper Sjöström","doi":"10.3389/fnsyn.2025.1548563","DOIUrl":"10.3389/fnsyn.2025.1548563","url":null,"abstract":"<p><p>Long-term plasticity at pyramidal cell to basket cell (PC → BC) synapses is important for the functioning of cortical microcircuits. It is well known that at neocortical PC → PC synapses, dendritic calcium (Ca²⁺) dynamics signal coincident pre-and postsynaptic spiking which in turn triggers long-term potentiation (LTP). However, the link between dendritic Ca²⁺ dynamics and long-term plasticity at PC → BC synapses of primary visual cortex (V1) is not as well known. Here, we explored if PC → BC synaptic plasticity in developing V1 is sensitive to postsynaptic spiking. Two-photon (2P) Ca²⁺ imaging revealed that action potentials (APs) in dendrites of V1 layer-5 (L5) BCs back-propagated decrementally but actively to the location of PC → BC putative synaptic contacts. Pairing excitatory inputs with postsynaptic APs elicited dendritic Ca²⁺ supralinearities for pre-before-postsynaptic but not post-before-presynaptic temporal ordering, suggesting that APs could impact synaptic plasticity. In agreement, extracellular stimulation as well as high-throughput 2P optogenetic mapping of plasticity both revealed that pre-before-postsynaptic but not post-before-presynaptic pairing resulted in anti-Hebbian long-term depression (LTD). Our results demonstrate that V1 BC dendritic Ca²⁺ nonlinearities and synaptic plasticity at PC → BC connections are both sensitive to somatic spiking.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"17 ","pages":"1548563"},"PeriodicalIF":2.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556630","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":"β-adrenergic receptor-induced E-S potentiation in the dorsal and ventral hippocampus.","authors":"George Trompoukis, Athina Miliou, Costas Papatheodoropoulos","doi":"10.3389/fnsyn.2024.1511485","DOIUrl":"https://doi.org/10.3389/fnsyn.2024.1511485","url":null,"abstract":"<p><p>β-adrenergic receptors (β-ARs) play a critical role in modulating learning, memory, emotionality, and long-term synaptic plasticity. Recent studies indicate that β-ARs are necessary for long-term potentiation (LTP) induction in the ventral hippocampus under moderate synaptic activation conditions that do not typically induce LTP. To explore potential dorsoventral differences in β-AR-mediated effects, we applied the β-AR agonist isoproterenol (10 μM, 30 min) to dorsal and ventral hippocampal slices, recording field excitatory postsynaptic potentials (fEPSPs) and population spikes (PSs) from the CA1 region. Isoproterenol induced robust, long-lasting PS increases, with effects three times greater in the dorsal compared to the ventral hippocampus. Isoproterenol did not significantly affect fEPSP in either segment of the hippocampus, leading to strong excitatory-to-spike (E-S) potentiation-twice as large as that in the ventral hippocampus. E-S potentiation was not associated with significant paired-pulse inhibition changes in either hippocampal segment. These differences do not appear to result from β1-AR expression levels, as they are comparable across dorsal and ventral hippocampal regions. Overall, the findings suggest that β-AR activation enhances the dorsal hippocampus's role during stress, facilitating heightened alertness, rapid spatial information processing, and effective navigation necessary for \"fight-or-flight\" responses.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"16 ","pages":"1511485"},"PeriodicalIF":2.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931380","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: Role of protein palmitoylation in synaptic plasticity and neuronal differentiation, volume II.","authors":"Kevin P Koster, William N Green","doi":"10.3389/fnsyn.2024.1473989","DOIUrl":"https://doi.org/10.3389/fnsyn.2024.1473989","url":null,"abstract":"","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"16 ","pages":"1473989"},"PeriodicalIF":2.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11420002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344951","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 short-term plasticity of VIP interneurons in motor cortex.","authors":"Amanda R McFarlan, Isabella Gomez, Christina Y C Chou, Adam Alcolado, Rui Ponte Costa, P Jesper Sjöström","doi":"10.3389/fnsyn.2024.1433977","DOIUrl":"https://doi.org/10.3389/fnsyn.2024.1433977","url":null,"abstract":"<p><p>Short-term plasticity is an important feature in the brain for shaping neural dynamics and for information processing. Short-term plasticity is known to depend on many factors including brain region, cortical layer, and cell type. Here we focus on vasoactive-intestinal peptide (VIP) interneurons (INs). VIP INs play a key disinhibitory role in cortical circuits by inhibiting other IN types, including Martinotti cells (MCs) and basket cells (BCs). Despite this prominent role, short-term plasticity at synapses to and from VIP INs is not well described. In this study, we therefore characterized the short-term plasticity at inputs and outputs of genetically targeted VIP INs in mouse motor cortex. To explore inhibitory to inhibitory (I → I) short-term plasticity at layer 2/3 (L2/3) VIP IN outputs onto L5 MCs and BCs, we relied on a combination of whole-cell recording, 2-photon microscopy, and optogenetics, which revealed that VIP IN→MC/BC synapses were consistently short-term depressing. To explore excitatory (E) → I short-term plasticity at inputs to VIP INs, we used extracellular stimulation. Surprisingly, unlike VIP IN outputs, E → VIP IN synapses exhibited heterogeneous short-term dynamics, which we attributed to the target VIP IN cell rather than the input. Computational modeling furthermore linked the diversity in short-term dynamics at VIP IN inputs to a wide variability in probability of release. Taken together, our findings highlight how short-term plasticity at VIP IN inputs and outputs is specific to synapse type. We propose that the broad diversity in short-term plasticity of VIP IN inputs forms a basis to code for a broad range of contrasting signal dynamics.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"16 ","pages":"1433977"},"PeriodicalIF":2.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11390561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142284293","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 in brain diseases, from the genetic to the functional level, volume II.","authors":"Laura Jiménez-Sánchez, Tak Pan Wong, Alberto Ouro","doi":"10.3389/fnsyn.2024.1470791","DOIUrl":"https://doi.org/10.3389/fnsyn.2024.1470791","url":null,"abstract":"","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"16 ","pages":"1470791"},"PeriodicalIF":2.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11387669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142284292","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 <i>Wingless</i> planar cell polarity pathway is essential for optimal activity-dependent synaptic plasticity.","authors":"Carihann Dominicci-Cotto, Mariam Vazquez, Bruno Marie","doi":"10.3389/fnsyn.2024.1322771","DOIUrl":"10.3389/fnsyn.2024.1322771","url":null,"abstract":"<p><p>From fly to man, the Wingless (Wg)/Wnt signaling molecule is essential for both the stability and plasticity of the nervous system. The <i>Drosophila</i> neuromuscular junction (NMJ) has proven to be a useful system for deciphering the role of Wg in directing activity-dependent synaptic plasticity (ADSP), which, in the motoneuron, has been shown to be dependent on both the canonical and the noncanonical calcium Wg pathways. Here we show that the noncanonical planar cell polarity (PCP) pathway is an essential component of the Wg signaling system controlling plasticity at the motoneuron synapse. We present evidence that disturbing the PCP pathway leads to a perturbation in ADSP. We first show that a PCP-specific allele of <i>disheveled</i> (<i>dsh</i>) affects the <i>de novo</i> synaptic structures produced during ADSP. We then show that the Rho GTPases downstream of Dsh in the PCP pathway are also involved in regulating the morphological changes that take place after repeated stimulation. Finally, we show that Jun kinase is essential for this phenomenon, whereas we found no indication of the involvement of the transcription factor complex AP1 (Jun/Fos). This work shows the involvement of the neuronal PCP signaling pathway in supporting ADSP. Because we find that AP1 mutants can perform ADSP adequately, we hypothesize that, upon Wg activation, the Rho GTPases and Jun kinase are involved locally at the synapse, in instructing cytoskeletal dynamics responsible for the appearance of the morphological changes occurring during ADSP.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"16 ","pages":"1322771"},"PeriodicalIF":2.8,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11021733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140864406","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 plasticity through a naturalistic lens","authors":"Charlotte Piette, Nicolas Gervasi, Laurent Venance","doi":"10.3389/fnsyn.2023.1250753","DOIUrl":"https://doi.org/10.3389/fnsyn.2023.1250753","url":null,"abstract":"From the myriad of studies on neuronal plasticity, investigating its underlying molecular mechanisms up to its behavioral relevance, a very complex landscape has emerged. Recent efforts have been achieved toward more naturalistic investigations as an attempt to better capture the synaptic plasticity underpinning of learning and memory, which has been fostered by the development of in vivo electrophysiological and imaging tools. In this review, we examine these naturalistic investigations, by devoting a first part to synaptic plasticity rules issued from naturalistic in vivo-like activity patterns. We next give an overview of the novel tools, which enable an increased spatio-temporal specificity for detecting and manipulating plasticity expressed at individual spines up to neuronal circuit level during behavior. Finally, we put particular emphasis on works considering brain-body communication loops and macroscale contributors to synaptic plasticity, such as body internal states and brain energy metabolism.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"84 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138590660","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}