Frontiers in Cellular Neuroscience最新文献

{"title":"Regional heterogeneity in the membrane properties of mouse striatal neurons","authors":"Nao Chuhma, Stephen Rayport","doi":"10.3389/fncel.2024.1412897","DOIUrl":"https://doi.org/10.3389/fncel.2024.1412897","url":null,"abstract":"The cytoarchitecture of the striatum is remarkably homogeneous, in contrast to the regional variation in striatal functions. Whether differences in the intrinsic membrane properties of striatal neurons contribute to regional heterogeneity has not been addressed systematically. We made recordings throughout the young adult mouse striatum under identical conditions, with synaptic input blocked, from four major striatal neuron types, namely, the two subtypes of spiny projection neurons (SPNs), cholinergic interneurons (ChIs), and fast-spiking GABAergic interneurons (FSIs), sampling at least 100 cells per cell type. Regional variation manifested across all cell types. All cell types in the nucleus accumbens (NAc) shell had higher input impedance and increased excitability. Cells in the NAc core were differentiated from the caudate-putamen (CPu) for both SPN subtypes by smaller action potentials and increased excitability. Similarity between the two SPN subtypes showed regional variation, differing more in the NAc than in the CPu. So, in the Str, both the intrinsic properties of interneurons and projection neurons are regionally heterogeneous, with the greatest difference between the NAc and CPu; greater excitability of NAc shell neurons may make the region more susceptible to activity-dependent plasticity.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141868987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural ensembles: role of intrinsic excitability and its plasticity","authors":"Christian Hansel, Rafael Yuste","doi":"10.3389/fncel.2024.1440588","DOIUrl":"https://doi.org/10.3389/fncel.2024.1440588","url":null,"abstract":"Synaptic connectivity defines groups of neurons that engage in correlated activity during specific functional tasks. These co-active groups of neurons form ensembles, the operational units involved in, for example, sensory perception, motor coordination and memory (then called an <jats:italic>engram</jats:italic>). Traditionally, ensemble formation has been thought to occur via strengthening of synaptic connections via long-term potentiation (LTP) as a plasticity mechanism. This synaptic theory of memory arises from the learning rules formulated by Hebb and is consistent with many experimental observations. Here, we propose, as an alternative, that the intrinsic excitability of neurons and its plasticity constitute a second, <jats:italic>non-synaptic</jats:italic> mechanism that could be important for the initial formation of ensembles. Indeed, enhanced neural excitability is widely observed in multiple brain areas subsequent to behavioral learning. In cortical structures and the amygdala, excitability changes are often reported as transient, even though they can last tens of minutes to a few days. Perhaps it is for this reason that they have been traditionally considered as modulatory, merely supporting ensemble formation by facilitating LTP induction, without further involvement in memory function (memory allocation hypothesis). We here suggest−based on two lines of evidence—that beyond modulating LTP allocation, enhanced excitability plays a more fundamental role in learning. First, enhanced excitability constitutes a signature of active ensembles and, due to it, subthreshold synaptic connections become suprathreshold in the absence of synaptic plasticity (<jats:italic>iceberg model</jats:italic>). Second, enhanced excitability promotes the propagation of dendritic potentials toward the soma and allows for enhanced coupling of EPSP amplitude (LTP) to the spike output (and thus ensemble participation). This <jats:italic>permissive gate model</jats:italic> describes a need for permanently increased excitability, which seems at odds with its traditional consideration as a short-lived mechanism. We propose that longer modifications in excitability are made possible by a low threshold for intrinsic plasticity induction, suggesting that excitability might be on/off-modulated at short intervals. Consistent with this, in cerebellar Purkinje cells, excitability lasts days to weeks, which shows that in some circuits the duration of the phenomenon is not a limiting factor in the first place. In our model, synaptic plasticity defines the information content received by neurons through the connectivity network that they are embedded in. However, the plasticity of cell-autonomous excitability could dynamically regulate the ensemble participation of individual neurons as well as the overall activity state of an ensemble.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141868988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impairment of synaptic plasticity in the primary somatosensory cortex in a model of diabetic mice","authors":"Nuria García-Magro, Alberto Mesa-Lombardo, Natali Barros-Zulaica, Ángel Nuñez","doi":"10.3389/fncel.2024.1444395","DOIUrl":"https://doi.org/10.3389/fncel.2024.1444395","url":null,"abstract":"Type 1 and type 2 diabetic patients experience alterations in the Central Nervous System, leading to cognitive deficits. Cognitive deficits have been also observed in animal models of diabetes such as impaired sensory perception, as well as deficits in working and spatial memory functions. It has been suggested that a reduction of insulin-like growth factor-I (IGF-I) and/or insulin levels may induce these neurological disorders. We have studied synaptic plasticity in the primary somatosensory cortex of young streptozotocin (STZ)-diabetic mice. We focused on the influence of reduced IGF-I brain levels on cortical synaptic plasticity. Unit recordings were conducted in layer 2/3 neurons of the primary somatosensory (S1) cortex in both control and STZ-diabetic mice under isoflurane anesthesia. Synaptic plasticity was induced by repetitive whisker stimulation. Results showed that repetitive stimulation of whiskers (8 Hz induction train) elicited a long-term potentiation (LTP) in layer 2/3 neurons of the S1 cortex of control mice. In contrast, the same induction train elicited a long-term depression (LTD) in STZ-diabetic mice that was dependent on NMDA and metabotropic glutamatergic receptors. The reduction of IGF-I brain levels in diabetes could be responsible of synaptic plasticity impairment, as evidenced by improved response facilitation in STZ-diabetic mice following the application of IGF-I. This hypothesis was further supported by immunochemical techniques, which revealed a reduction in IGF-I receptors in the layer 2/3 of the S1 cortex in STZ-diabetic animals. The observed synaptic plasticity impairments in STZ-diabetic animals were accompanied by decreased performance in a whisker discrimination task, along with reductions in IGF-I, GluR1, and NMDA receptors observed in immunochemical studies. In conclusion, impaired synaptic plasticity in the S1 cortex may stem from reduced IGF-I signaling, leading to decreased intracellular signal pathways and thus, glutamatergic receptor numbers in the cellular membrane.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141868989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired olfactory performance and anxiety-like behavior in a rat model of multiple sclerosis are associated with enhanced adenosine signaling in the olfactory bulb via A1R, A2BR, and A3R","authors":"Andjela Stekic, Milorad Dragic, Jelena Stanojevic, Marina Zaric Kontic, Ivana Stevanovic, Milica Zeljkovic Jovanovic, Katarina Mihajlovic, Nadezda Nedeljkovic","doi":"10.3389/fncel.2024.1407975","DOIUrl":"https://doi.org/10.3389/fncel.2024.1407975","url":null,"abstract":"The present study shows that animals with experimental autoimmune encephalomyelitis (EAE) exhibit olfactory dysfunction and impaired general cognitive abilities, as well as anxiety-like behavior. Olfactory dysfunction occurs on average at 2 dpi, well before the onset of the first motor signs of EAE (8–10 dpi). After the initial olfactory dysfunction, the EAE animals show a fluctuation in olfactory performance that resembles the relapsing–remitting course of human MS. The study also shows severe neuroinflammation in the olfactory bulb (OB), with numerous infiltrated CD4<jats:sup>+</jats:sup> T cells and peripheral macrophages in the superficial OB layers, marked microgliosis, and massive induction of TNF-α, IL-1β, and IL-6. Reduced tyrosine hydroxylase activity in the glomerular layer, pronounced granule cell atrophy, and reduced numbers of type B neuroblasts in the rostral migratory stream also indicate altered plasticity of the neuronal network in the OB. Considering the exceptionally high purinome expression in the OB, the possible involvement of purinergic signaling was also investigated. The study shows that macrophages infiltrating the OB overexpress A<jats:sub>3</jats:sub>R, while highly reactive microglia overexpress the adenosine-producing enzyme eN/CD73 as well as A<jats:sub>2B</jats:sub>R, A<jats:sub>3</jats:sub>R, and P2X<jats:sub>4</jats:sub>R. Given the simultaneous induction of complement component C3, the results suggest that the microglial cells develop a functional phenotype of phagocytizing microglia. The study also demonstrates transcriptional and translational upregulation of A<jats:sub>1</jats:sub>R in mitral and tufted cells, which likely influence resting network activity in OB and likely contribute to olfactory dysfunction in EAE. Overall, our study shows that olfactory dysfunction and altered social and cognitive behavior in EAE are associated with increased adenosine signaling via A<jats:sub>1</jats:sub>R, A<jats:sub>2B</jats:sub>R, and A<jats:sub>3</jats:sub>R.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141873114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potassium channels in animal models of post-traumatic stress disorder: mechanistic and therapeutic implications.","authors":"Ravi Philip Rajkumar","doi":"10.3389/fncel.2024.1441514","DOIUrl":"10.3389/fncel.2024.1441514","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frontiers | Potential role of endothelial progenitor cells in the pathogenesis and treatment of cerebral aneurysm","authors":"Jin Yu, Qian Du, Xiang Li, Wei Wei, Yuncun Fan, Jianjian Zhang, Jincao Chen","doi":"10.3389/fncel.2024.1456775","DOIUrl":"https://doi.org/10.3389/fncel.2024.1456775","url":null,"abstract":"Cerebral aneurysm (CA) is a significant health concern that results from pathological dilations of blood vessels in the brain and can lead to severe and potentially life-threatening conditions. While the pathogenesis of CA is complex, emerging studies suggest that endothelial progenitor cells (EPCs) play a crucial role. In this paper, we conducted a comprehensive literature review to investigate the potential role of EPCs in the pathogenesis and treatment of CA. Current research indicates that a decreased count and dysfunction of EPCs disrupt the balance between endothelial dysfunction and repair, thus increasing the risk of CA formation. Reversing these EPCs abnormalities may reduce the progression of vascular degeneration after aneurysm induction, indicating EPCs as a promising target for developing new therapeutic strategies to facilitate CA repair. This has motivated researchers to develop novel treatment options, including drug applications, endovascular-combined and tissue engineering therapies. Although preclinical studies have shown promising results, there is still a considerable way to go before clinical translation and eventual benefits for patients. Nonetheless, these findings offer hope for improving the treatment and management of this condition.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141931156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel autism-associated KCNB1 mutation dramatically slows Kv2.1 potassium channel activation, deactivation and inactivation","authors":"Rían W. Manville, Samantha D. Block, Claire L. Illeck, Jessica Kottmeier, Richard Sidlow, Geoffrey W. Abbott","doi":"10.3389/fncel.2024.1438101","DOIUrl":"https://doi.org/10.3389/fncel.2024.1438101","url":null,"abstract":"<jats:italic>KCNB1</jats:italic>, on human chromosome 20q13.3, encodes the alpha subunit of the Kv2.1 voltage gated potassium channel. Kv2.1 is ubiquitously expressed throughout the brain and is critical in controlling neuronal excitability, including in the hippocampus and pyramidal neurons. Human <jats:italic>KCNB1</jats:italic> mutations are known to cause global development delay or plateauing, epilepsy, and behavioral disorders. Here, we report a sibling pair with developmental delay, absence seizures, autism spectrum disorder, hypotonia, and dysmorphic features. Whole exome sequencing revealed a heterozygous variant of uncertain significance (c. 342 C&amp;gt;A), p. (S114R) in <jats:italic>KCNB1</jats:italic>, encoding a serine to arginine substitution (S114R) in the N-terminal cytoplasmic region of Kv2.1. The siblings’ father demonstrated autistic features and was determined to be an obligate <jats:italic>KCNB1</jats:italic> c. 342 C&amp;gt;A carrier based on familial genetic testing results. Functional investigation of Kv2.1-S114R using cellular electrophysiology revealed slowing of channel activation, deactivation, and inactivation, resulting in increased net current after longer membrane depolarizations. To our knowledge, this is the first study of its kind that compares the presentation of siblings each with a <jats:italic>KCNB1</jats:italic> disorder. Our study demonstrates that Kv2.1-S114R has profound cellular and phenotypic consequences. Understanding the mechanisms underlying <jats:italic>KCNB1</jats:italic>-linked disorders aids clinicians in diagnosis and treatment and provides potential therapeutic avenues to pursue.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141869133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroinflammation in Parkinson’s disease: focus on the relationship between miRNAs and microglia","authors":"Ke Xu, Yuan Li, Yan Zhou, Yu Zhang, Yue Shi, Chengguang Zhang, Yan Bai, Shun Wang","doi":"10.3389/fncel.2024.1429977","DOIUrl":"https://doi.org/10.3389/fncel.2024.1429977","url":null,"abstract":"Parkinson’s disease (PD) is a prevalent neurodegenerative disorder that affects the central nervous system (CNS). Neuroinflammation is a crucial factor in the pathological advancement of PD. PD is characterized by the presence of activated microglia and increased levels of proinflammatory factors, which play a crucial role in its pathology. During the immune response of PD, microglia regulation is significantly influenced by microRNA (miRNA). The excessive activation of microglia, persistent neuroinflammation, and abnormal polarization of macrophages in the brain can be attributed to the dysregulation of certain miRNAs. Additionally, there are miRNAs that possess the ability to inhibit neuroinflammation. miRNAs, which are small non-coding epigenetic regulators, have the ability to modulate microglial activity in both normal and abnormal conditions. They also have a significant impact on promoting communication between neurons and microglia.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141772122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A decrease in Fkbp52 alters autophagosome maturation and A152T-tau clearance in vivo","authors":"Emilie Lesport, Lucie Commeau, Mélanie Genet, Etienne-Emile Baulieu, Marcel Tawk, Julien Giustiniani","doi":"10.3389/fncel.2024.1425222","DOIUrl":"https://doi.org/10.3389/fncel.2024.1425222","url":null,"abstract":"The failure of the autophagy-lysosomal pathway to clear the pathogenic forms of Tau exacerbates the pathogenesis of tauopathies. We have previously shown that the immunophilin FKBP52 interacts both physically and functionally with Tau, and that a decrease in FKBP52 protein levels is associated with Tau deposition in affected human brains. We have also shown that FKBP52 is physiologically present within the lysosomal system in healthy human neurons and that a decrease in FKBP52 expression alters perinuclear lysosomal positioning and Tau clearance during Tau-induced proteotoxic stress <jats:italic>in vitro</jats:italic>. In this study, we generate a zebrafish <jats:italic>fkbp4</jats:italic> loss of function mutant and show that axonal retrograde trafficking of Lamp1 vesicles is altered in this mutant. Moreover, using our transgenic <jats:italic>HuC::mCherry-EGFP-LC3</jats:italic> line, we demonstrate that the autophagic flux is impaired in <jats:italic>fkbp4</jats:italic> mutant embryos, suggesting a role for Fkbp52 in the maturation of autophagic vesicles. Alterations in both axonal transport and autophagic flux are more evident in heterozygous rather than homozygous <jats:italic>fkbp4</jats:italic> mutants. Finally, taking advantage of the previously described A152T-Tau transgenic fish, we show that the clearance of pathogenic A152T-Tau mutant proteins is slower in <jats:italic>fkbp4</jats:italic><jats:sup>+/−</jats:sup> mutants in comparison to <jats:italic>fkbp4</jats:italic><jats:sup>+/+</jats:sup> larvae. Altogether, these results indicate that Fkbp52 is required for the normal trafficking and maturation of lysosomes and autophagic vacuoles along axons, and that its decrease is sufficient to hinder the clearance of pathogenic Tau <jats:italic>in vivo</jats:italic>.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141772123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling riboflavin transporter deficiency type 2: from iPSC-derived motoneurons to iPSC-derived astrocytes","authors":"Valentina Magliocca, Angela Lanciotti, Elena Ambrosini, Lorena Travaglini, Veronica D’Ezio, Valentina D’Oria, Stefania Petrini, Michela Catteruccia, Keith Massey, Marco Tartaglia, Enrico Bertini, Tiziana Persichini, Claudia Compagnucci","doi":"10.3389/fncel.2024.1440555","DOIUrl":"https://doi.org/10.3389/fncel.2024.1440555","url":null,"abstract":"IntroductionRiboflavin transporter deficiency type 2 (RTD2) is a rare neurodegenerative autosomal recessive disease caused by mutations in the SLC52A2 gene encoding the riboflavin transporters, RFVT2. Riboflavin (Rf) is the precursor of FAD (flavin adenine dinucleotide) and FMN (flavin mononucleotide), which are involved in different redox reactions, including the energetic metabolism processes occurring in mitochondria. To date, human induced pluripotent stem cells (iPSCs) have given the opportunity to characterize RTD2 motoneurons, which reflect the most affected cell type. Previous works have demonstrated mitochondrial and peroxisomal altered energy metabolism as well as cytoskeletal derangement in RTD2 iPSCs and iPSC-derived motoneurons. So far, no attention has been dedicated to astrocytes.Results and discussionHere, we demonstrate that <jats:italic>in vitro</jats:italic> differentiation of astrocytes, which guarantee trophic and metabolic support to neurons, from RTD2 iPSCs is not compromised. These cells do not exhibit evident morphological differences nor significant changes in the survival rate when compared to astrocytes derived from iPSCs of healthy individuals. These findings indicate that differently from what had previously been documented for neurons, RTD2 does not compromise the morpho-functional features of astrocytes.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141772233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}