Frontiers in Cellular Neuroscience最新文献

{"title":"Studying the mechanisms of neurodegeneration: <i>C. elegans</i> advantages and opportunities.","authors":"Angie K Torres, Rodrigo G Mira, Cristina Pinto, Nibaldo C Inestrosa","doi":"10.3389/fncel.2025.1559151","DOIUrl":"https://doi.org/10.3389/fncel.2025.1559151","url":null,"abstract":"<p><p><i>Caenorhabditis elegans</i> has been widely used as a model organism in neurodevelopment for several decades due to its simplicity, rapid growth, short life cycle, transparency, and rather simple genetics. It has been useful in modeling neurodegenerative diseases by the heterologous expression of the major proteins that form neurodegenerative-linked aggregates such as amyloid-<i>β</i> peptide, tau protein, and <i>α</i>-synuclein, among others. Furthermore, chemical treatments as well as the existence of several interference RNA libraries, transgenic worm lines, and the possibility of generating new transgenic strains create a magnificent range of possible tools to study the signaling pathways that could confer protection against protein aggregates or, on the contrary, are playing a detrimental role. In this review, we summarize the different <i>C. elegans</i> models of neurodegenerative diseases with a focus on Alzheimer's and Parkinson's diseases and how genetic tools could be used to dissect the signaling pathways involved in their pathogenesis mentioning several examples. Finally, we discuss the use of pharmacological agents in <i>C. elegans</i> models that could help to study these disease-associated signaling pathways and the powerful combinations of experimental designs with genetic tools. This review highlights the advantages of <i>C. elegans</i> as a valuable intermediary between <i>in vitro</i> and mammalian <i>in vivo</i> models in the development of potential new therapies.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1559151"},"PeriodicalIF":4.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11979225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990924","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":"Striatal function scrutinized through the PAN-TAN-FSI triumvirate.","authors":"Paul Apicella, Anne-Caroline Martel, Kevin Marche","doi":"10.3389/fncel.2025.1572657","DOIUrl":"10.3389/fncel.2025.1572657","url":null,"abstract":"<p><p>Understanding the information encoded by distinct components of the neuronal circuitry in the striatum represents an avenue for elucidating the role of this subcortical region in adaptive behavior and its dysfunction in pathological conditions. In behaving animals, conventional single neuron recordings generally differentiated between three main electrophysiologically identified neuron subtypes in the striatum, referred to as phasically active neurons (PANs), tonically active neurons (TANs), and fast-spiking interneurons (FSIs), assumed to correspond to GABAergic spiny projection neurons, cholinergic interneurons, and parvalbumin-containing GABAergic interneurons, respectively. Considerable research has been devoted to exploring the behavior-related activities of neurons classified electrophysiologically into PANs, TANs, and FSIs in animals engaged in task performance, mostly monkeys. Although precise neuron identification remains a major challenge, such electrophysiological studies have provided insights into the functional properties of presumed distinct striatal neuronal populations. In this review, we will focus on current ideas about the functions subserved by these neuron subtypes, emphasizing their link to specific aspects of behaviors. We will also underline the issues that are yet to be resolved regarding the classification of striatal neurons into distinct subgroups which emphasize the importance of considering the potential overlap among electrophysiological characteristics and the molecular diversity of neuron types in the striatum.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1572657"},"PeriodicalIF":4.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810907","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":"Corrigendum: Epothilone B facilitates peripheral nerve regeneration by promoting autophagy and migration in Schwann cells.","authors":"Jianhua Zhou, Shengyou Li, Jianbo Gao, Yawei Hu, Shaochu Chen, Xinle Luo, Hao Zhang, Zhuojing Luo, Jinghui Huang","doi":"10.3389/fncel.2025.1574709","DOIUrl":"https://doi.org/10.3389/fncel.2025.1574709","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fncel.2020.00143.].</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1574709"},"PeriodicalIF":4.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810906","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":"Synapses mediate the effects of different types of stress on working memory: a brain-inspired spiking neural network study.","authors":"Chengcheng Du, Yinqian Sun, Jihang Wang, Qian Zhang, Yi Zeng","doi":"10.3389/fncel.2025.1534839","DOIUrl":"10.3389/fncel.2025.1534839","url":null,"abstract":"<p><p>Acute stress results from sudden short-term events, and individuals need to quickly adjust their physiological and psychological to re-establish balance. Chronic stress, on the other hand, results in long-term physiological and psychological burdens due to the continued existence of stressors, making it difficult for individuals to recover and prone to pathological symptoms. Both types of stress can affect working memory and change cognitive function. In this study, we explored the impact of acute and chronic stress on synaptic modulation using a biologically inspired, data-driven rodent prefrontal neural network model. The model consists of a specific number of excitatory and inhibitory neurons that are connected through AMPA, NMDA, and GABA synapses. The study used a short-term recall to simulate working memory tasks and assess the ability of neuronal populations to maintain information over time. The results showed that acute stress can enhance working memory information retention by enhancing AMPA and NMDA synaptic currents. In contrast, chronic stress reduces dendritic spine density and weakens the regulatory effect of GABA currents on working memory tasks. In addition, this structural damage can be complemented by strong connections between excitatory neurons with the same selectivity. These findings provide a reference scheme for understanding the neural basis of working memory under different stress conditions.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1534839"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771520","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":"Astroglia's role in synchronized spontaneous neuronal activity: from physiology to pathology.","authors":"Aswathy Ammothumkandy, Alisha Cayce, Mohammad Shariq, Michael A Bonaguidi","doi":"10.3389/fncel.2025.1544460","DOIUrl":"10.3389/fncel.2025.1544460","url":null,"abstract":"<p><p>The nervous system relies on a balance of excitatory and inhibitory signals. Aberrant neuronal hyperactivity is a pathological phenotype associated with several neurological disorders, with its most severe effects observed in epilepsy patients. This review explores the literature on spontaneous synchronized neuronal activity, its physiological role, and its aberrant forms in disease. Emphasizing the importance of targeting underlying disease mechanisms beyond traditional neuron-focused therapies, the review delves into the role of astroglia in epilepsy progression. We detail how astroglia transitions from a normal to a pathological state, leading to epileptogenic seizures and cognitive decline. Astroglia activity is correlated with epileptiform activity in both animal models and human tissue, indicating their potential role in seizure induction and modulation. Understanding astroglia's dual beneficial and detrimental roles could lead to novel treatments for epilepsy and other neurological disorders with aberrant neuronal activity as the underlying disease substrate.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1544460"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771576","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":"Chemogenetic activation of Gq signaling modulates dendritic development of cortical neurons in a time- and layer-specific manner.","authors":"Ina Köhler, Lisa Marie Rennau, Adriana Rehm, Julia Große, Steffen Gonda, Andrea Räk, Christian Riedel, Petra Wahle","doi":"10.3389/fncel.2025.1524470","DOIUrl":"10.3389/fncel.2025.1524470","url":null,"abstract":"<p><p>Designer receptors exclusively activated by designer drugs (DREADDs) are established tools for modulating neuronal activity. Calcium-mobilizing DREADD hM3Dq has been widely used to enhance neuronal activity. hM3Dq activates the Gq protein signaling cascade and mimics the action of native Gq protein-coupled receptors such as muscarinic m1 and m3 receptors leading to calcium release from intracellular storages. Depolarization evoked by increased intracellular calcium levels is an important factor for neuronal maturation. Here, we used repetitive activation of biolistically overexpressed hM3Dq to increase the activity of individual neurons differentiating in organotypic slice cultures of rat visual cortex. HM3Dq was activated by 3 μM clozapine-N-oxide (CNO) dissolved in H₂O. Transfectants expressing hM3Dq mock-stimulated with H₂O served as batch-internal controls. Pyramidal cells and multipolar interneurons were analyzed after treatment from DIV 5-10, DIV 10-20, and DIV 15-20 to investigate if Gq signaling is involved in dendritic maturation. Results show that hM3Dq activation accelerated the maturation of apical dendrites of L2/3 pyramidal cells in the early, but no longer in the later time windows. In contrast, dendritic dimensions of L5/6 pyramidal cells and interneurons were not altered at DIV 10. These findings suggest a growth-promoting role of activated Gq signaling selectively for early postnatal L2/3 pyramidal cells. Unexpectedly, hM3Dq activation from DIV 10-20 reduced the dendritic complexity of L5/6 pyramidal cells and multipolar interneurons. Together, results suggest a role of Gq signaling for neuronal differentiation and support evidence that it may also limit dendritic growth.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1524470"},"PeriodicalIF":4.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771517","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":"Estimates of quantal synaptic parameters in light of more complex vesicle pool models.","authors":"Simone Brachtendorf, Grit Bornschein, Hartmut Schmidt","doi":"10.3389/fncel.2025.1556360","DOIUrl":"10.3389/fncel.2025.1556360","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1556360"},"PeriodicalIF":4.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763358","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":"Association between cognitive functioning and microbiota-gut-brain axis mediators in a memory clinic population.","authors":"Claudio Singh Solorzano, Cristina Festari, Peppino Mirabelli, Elisa Mombelli, Luigi Coppola, Delia Luongo, Daniele Naviglio, Andrea Soricelli, Giulia Quattrini, Marco Salvatore, Michela Pievani, Annamaria Cattaneo, Giovanni B Frisoni, Moira Marizzoni","doi":"10.3389/fncel.2025.1550333","DOIUrl":"10.3389/fncel.2025.1550333","url":null,"abstract":"","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1550333"},"PeriodicalIF":4.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718220","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":"Translational profiling reveals novel gene expression changes in the direct and indirect pathways in a mouse model of levodopa induced dyskinesia.","authors":"Sabika Jafri, Mahdi Ghani, Natalie Stickle, Carl Virtanen, Lili-Naz Hazrati, Naomi P Visanji","doi":"10.3389/fncel.2024.1477511","DOIUrl":"10.3389/fncel.2024.1477511","url":null,"abstract":"<p><strong>Introduction: </strong>The molecular mechanisms underlying L-dihydroxyphenylalanine (LDOPA) induced dyskinesia in Parkinson's disease are poorly understood. Here we employ two transgenic mouse lines, combining translating ribosomal affinity purification (TRAP) with bacterial artificial chromosome expression (Bac), to selectively isolate RNA from either DRD1A expressing striatonigral, or DRD2 expressing striatopallidal medium spiny neurons (MSNs) of the direct and indirect pathways respectively, to study changes in translational gene expression following repeated LDOPA treatment.</p><p><strong>Methods: </strong>6-OHDA lesioned DRD1A and DRD2 BacTRAP mice were treated with either saline or LDOPA bi-daily for 21 days over which time they developed abnormal involuntary movements reminiscent of dyskinesia. On day 22, all animals received LDOPA 40min prior to sacrifice. The striatum of the lesioned hemisphere was dissected and subject to TRAP. Extracted ribosomal RNA was amplified, purified, and gene expression was quantified using microarray.</p><p><strong>Results: </strong>One hundred ninety-five significantly varying transcripts were identified among the four treatment groups. Pathway analysis revealed an overrepresentation of calcium signaling and long-term potentiation in the DRD1A expressing MSNs of the direct pathway, with significant involvement of long-term depression in the DRD2 expressing MSNs of the indirect pathway following chronic treatment with LDOPA. Several MAPK associated genes (<i>NR4A1, GADD45G, STMN1, FOS</i>, and <i>DUSP1</i>) differentiated the direct and indirect pathways following both acute and chronic LDOPA treatment. However, the MAPK pathway activator <i>PAK1</i> was downregulated in the indirect pathway and upregulated in the direct pathway, strongly suggesting a role for <i>PAK1</i> in regulating the opposing effects of LDOPA on these two pathways in dyskinesia.</p><p><strong>Discussion: </strong>Future studies will assess the potential of targeting these genes and pathways to prevent the development of LDOPA-induced dyskinesia.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1477511"},"PeriodicalIF":4.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718206","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":"Characterize neuronal responses to natural movies in the mouse superior colliculus.","authors":"Ya-Tang Li","doi":"10.3389/fncel.2025.1558504","DOIUrl":"10.3389/fncel.2025.1558504","url":null,"abstract":"<p><p>While artificial stimuli have been widely used in visual neuroscience and have significantly advanced our understanding of visual processing, they differ dramatically from the natural scenes that animals encounter in the wild. How natural stimuli are encoded in the superior colliculus (SC) and how neuronal responses to artificial and natural stimuli are related remain poorly understood. Here I applied two-photon calcium imaging to record neuronal activity in the mouse superficial SC in response to natural movies. An unsupervised learning algorithm grouped recorded neurons into 16 clusters based on their response patterns. Each cluster exhibited distinct temporal profiles, which arose from differences in both receptive field coverage and how neurons encode local visual features. Interestingly, I found a strong correlation between neuronal responses to natural movies and functional properties previously characterized using artificial stimuli. This suggests that the SC maintains a stable neural representation of visual information that is largely independent of the types of visual stimuli. Furthermore, neuronal responses to natural movies varied with depth within the superficial SC and across genetically defined neuronal types. These findings bridge the gap between our understanding of responses to artificial and natural stimuli, providing new insights into visual processing in the SC.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1558504"},"PeriodicalIF":4.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11933010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708220","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}