Hua Bai, Trisha Naidu, James B Anderson, Hector Montemayor, Camie Do, Lina Ni
{"title":"The impacts of hypertonic conditions on <i>Drosophila</i> larval cool cells.","authors":"Hua Bai, Trisha Naidu, James B Anderson, Hector Montemayor, Camie Do, Lina Ni","doi":"10.3389/fncel.2024.1347460","DOIUrl":"10.3389/fncel.2024.1347460","url":null,"abstract":"<p><p><i>Drosophila melanogaster</i> exhibits multiple highly sophisticated temperature-sensing systems, enabling its effective response and navigation to temperature changes. Previous research has identified three dorsal organ cool cells (DOCCs) in fly larvae, consisting of two A-type and one B-type cell with distinct calcium dynamics. When subjected to hypertonic conditions, calcium imaging shows that A-type DOCCs maintain their responses to cool temperatures. In contrast, a subset of B-type DOCCs does not exhibit detectable GCaMP baseline signals, and the remaining detectable B-type DOCCs exhibit reduced temperature responses. The activation of both A-type and B-type DOCCs depends on the same members of the ionotropic receptor (IR) family: IR21a, IR93a, and IR25a. A-type DOCCs exhibit a higher somal level of IR93a than B-type DOCCs. Overexpression of <i>Ir93a</i> restores B-type calcium responses to cool temperatures, but not the proportion of B-type cells with a detectable GCaMP baseline, in a hypertonic environment, suggesting a selective role of IR93a in maintaining the temperature responses under hypertonic conditions. Our findings identify a novel function of B-type DOCCs in integrating temperature and tonic stimuli.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1347460"},"PeriodicalIF":4.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389277","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}
Ji On Park, Namgue Hong, Min Young Lee, Jin-Chul Ahn
{"title":"Photobiomodulation regulates astrocyte activity and ameliorates scopolamine-induced cognitive behavioral decline.","authors":"Ji On Park, Namgue Hong, Min Young Lee, Jin-Chul Ahn","doi":"10.3389/fncel.2024.1448005","DOIUrl":"10.3389/fncel.2024.1448005","url":null,"abstract":"<p><strong>Introduction: </strong>The pathophysiological mechanism of Alzheimer's disease (AD) has not been clearly identified, and effective treatment methods have not yet been established. Scopolamine causes cholinergic dysfunction in the brain, including the accumulation of amyloid-beta plaques, thereby increasing oxidative stress and neuroinflammation, mimicking AD. Glial cells such as astrocytes have recently been identified as possible biomarkers for AD. Photobiomodulation (PBM) elicits a beneficial biological response in cells and tissues. PBM effects on the central nervous system (CNS) have been widely researched, including effects on astrocyte activity.</p><p><strong>Methods: </strong>In the present study, PBM was performed using light at the near-infrared wavelength of 825 nm. The Morris water maze and Y-maze tests were employed to evaluate cognitive function decline in a scopolamine-induced memory dysfunction model and its improvement with PBM. In addition, alteration of the mitogen-activated protein kinase (MAPK) pathway and immunofluorescence expression levels of active astrocytes were observed in the hippocampus, which is one of the areas affected by AD, to evaluate the mechanism of action of PBM.</p><p><strong>Results: </strong>A reduction in the neuronal cell death in the hippocampus caused by scopolamine was observed with PBM. Moreover, alteration of a MAPK pathway-related marker and changes in glial fibrillary acidic protein (an active astrocyte marker) expression were observed in the PBM-treated group. Finally, significant correlations between functional and histological results were found, validating the results.</p><p><strong>Discussion: </strong>These findings indicate the possibility of behavioral and histological improvement due to PBM in scopolamine-induced CNS alteration, which mimics AD. This improvement could be related to neuroinflammatory modulation and altered astrocyte activity.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1448005"},"PeriodicalIF":4.2,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380468","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}
Lorenzo Santucci, Sara Bernardi, Rachele Vivarelli, Filippo Maria Santorelli, Maria Marchese
{"title":"Glucose metabolism impairment as a hallmark of progressive myoclonus epilepsies: a focus on neuronal ceroid lipofuscinoses.","authors":"Lorenzo Santucci, Sara Bernardi, Rachele Vivarelli, Filippo Maria Santorelli, Maria Marchese","doi":"10.3389/fncel.2024.1445003","DOIUrl":"10.3389/fncel.2024.1445003","url":null,"abstract":"<p><p>Glucose is the brain's main fuel source, used in both energy and molecular production. Impaired glucose metabolism is associated with adult and pediatric neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), GLUT1 deficiency syndrome, and progressive myoclonus epilepsies (PMEs). PMEs, a group of neurological disorders typical of childhood and adolescence, account for 1% of all epileptic diseases in this population worldwide. Diffuse glucose hypometabolism is observed in the brains of patients affected by PMEs such as Lafora disease (LD), dentatorubral-pallidoluysian (DRPLA) atrophy, Unverricht-Lundborg disease (ULD), and myoclonus epilepsy with ragged red fibers (MERRFs). PMEs also include neuronal ceroid lipofuscinoses (NCLs), a subgroup in which lysosomal and autophagy dysfunction leads to progressive loss of vision, brain atrophy, and cognitive decline. We examine the role of impaired glucose metabolism in neurodegenerative diseases, particularly in the NCLs. Our literature review, which includes findings from case reports and animal studies, reveals that glucose hypometabolism is still poorly characterized both <i>in vitro</i> and <i>in vivo</i> in the different NCLs. Better identification of the glucose metabolism pathway impaired in the NCLs may open new avenues for evaluating the therapeutic potential of anti-diabetic agents in this population and thus raise the prospect of a therapeutic approach able to delay or even halt disease progression.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"18 ","pages":"1445003"},"PeriodicalIF":4.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371380","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}
Parker J. Ellingson, Yousif O. Shams, Jessica R. Parker, Ronald L. Calabrese, Gennady S. Cymbalyuk
{"title":"Multistability of bursting rhythms in a half-center oscillator and the protective effects of synaptic inhibition","authors":"Parker J. Ellingson, Yousif O. Shams, Jessica R. Parker, Ronald L. Calabrese, Gennady S. Cymbalyuk","doi":"10.3389/fncel.2024.1395026","DOIUrl":"https://doi.org/10.3389/fncel.2024.1395026","url":null,"abstract":"For animals to meet environmental challenges, the activity patterns of specialized oscillatory neural circuits, central pattern generators (CPGs), controlling rhythmic movements like breathing and locomotion, are adjusted by neuromodulation. As a representative example, the leech heartbeat is controlled by a CPG driven by two pairs of mutually inhibitory interneurons, heart interneuron (HN) half-center oscillators (HCO). Experiments and modeling indicate that neuromodulation of HCO navigates this CPG between dysfunctional regimes by employing a co-regulating inverted relation; reducing Na<jats:sup>+</jats:sup>/K<jats:sup>+</jats:sup> pump current and increasing hyperpolarization-activated (h-) current. Simply reducing pump activity or increasing h-current leads to either seizure-like bursting or an asymmetric bursting dysfunctional regime, respectively. Here, we demonstrate through modeling that, alongside this coregulation path, a new bursting regime emerges. Both regimes fulfill the criteria for functional bursting activity. Although the cycle periods and burst durations of these patterns are roughly the same, the new one exhibits an intra-burst spike frequency that is twice as high as the other. This finding suggests that neuromodulation could introduce additional functional regimes with higher spike frequency, and thus more effective synaptic transmission to motor neurons. We found that this new regime co-exists with the original bursting. The HCO can be switched between them by a short pulse of excitatory or inhibitory conductance. In this domain of coexisting functional patterns, an isolated cell model exhibits only one regime, a severely dysfunctional plateau-containing, seizure-like activity. This aligns with widely reported notion that deficiency of inhibition can cause seizures and other dysfunctional neural activities. We show that along the coregulation path of neuromodulation, the high excitability of the single HNs induced by myomodulin is harnessed by mutually inhibitory synaptic interactions of the HCO into the functional bursting pattern.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"17 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260208","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}
Xiangtian Ji, Xin Chen, Guozhong Lin, Kaiming Ma, Junhua Yang, Xiaofang Zhao, Suhua Chen, Jun Yang
{"title":"Discovery of GJC1 as a prognostic biomarker in glioma cells: insights into its cell-cycle relationship and differential expression in non-neuronal cells","authors":"Xiangtian Ji, Xin Chen, Guozhong Lin, Kaiming Ma, Junhua Yang, Xiaofang Zhao, Suhua Chen, Jun Yang","doi":"10.3389/fncel.2024.1440409","DOIUrl":"https://doi.org/10.3389/fncel.2024.1440409","url":null,"abstract":"BackgroundGliomas, originating from the most common non-neuronal cells in the brain (glial cells), are the most common brain tumors and are associated with high mortality and poor prognosis. Glioma cells exhibit a tendency to disrupt normal cell-cycle regulation, leading to abnormal proliferation and malignant growth. This study investigated the predictive potential of <jats:italic>GJC1</jats:italic> in gliomas and explored its relationship with the cell cycle.MethodsRetrospective analysis of RNA-seq and single-cell sequencing data was conducted using the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. The differential expression of <jats:italic>GJC1</jats:italic> in gliomas with various pathological features and in different non-neuronal cell groups was analyzed. Functional data were examined using gene set variation analysis (GSVA). Furthermore, CellMiner was used to evaluate the relationship between <jats:italic>GJC1</jats:italic> expression and predicted treatment response across these databases.Results<jats:italic>GJC1</jats:italic> expression was enriched in high-grade gliomas and 1p/19q non-codeletion gliomas. <jats:italic>GJC1</jats:italic> enrichment was observed in classical and mesenchymal subtypes within the TCGA glioma subtype group. In single-cell subgroup analysis, <jats:italic>GJC1</jats:italic> expression was higher in glioma tissues compared to other non-neuronal cells. Additionally, the TCGA classical subtype of glioma cells exhibited more <jats:italic>GJC1</jats:italic> expression than the other subgroups. <jats:italic>GJC1</jats:italic> emerged as an independent prognostic factor for overall survival in glioma. GSVA unveiled potential mechanisms by which <jats:italic>GJC1</jats:italic> may impact cell-cycle regulation in glioma. Finally, a significant correlation was observed between <jats:italic>GJC1</jats:italic> expression and the sensitivity of multiple anti-cancer drugs.ConclusionThese findings confirmed <jats:italic>GJC1</jats:italic> as a novel biomarker and provided insights into the differential gene expression in non-neuronal cells and the impact of the cell cycle on gliomas. Consequently, <jats:italic>GJC1</jats:italic> may be used to predict glioma prognosis and has potential therapeutic value.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"39 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260209","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}
Muhammad Tahir, Min Hwa Kang, Tae Ju Park, Jawad Ali, Kyonghwan Choe, Jun Sung Park, Myeong Ok Kim
{"title":"Multifaceted neuroprotective approach of Trolox in Alzheimer's disease mouse model: targeting Aβ pathology, neuroinflammation, oxidative stress, and synaptic dysfunction","authors":"Muhammad Tahir, Min Hwa Kang, Tae Ju Park, Jawad Ali, Kyonghwan Choe, Jun Sung Park, Myeong Ok Kim","doi":"10.3389/fncel.2024.1453038","DOIUrl":"https://doi.org/10.3389/fncel.2024.1453038","url":null,"abstract":"Alzheimer's disease (AD) is a progressive neurodegenerative disorder pathologically characterized by the deposition of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs) in the brain. The accumulation of these aggregated proteins causes memory and synaptic dysfunction, neuroinflammation, and oxidative stress. This research study is significant as it aims to assess the neuroprotective properties of vitamin E (VE) analog Trolox in an Aβ<jats:sub>1 − 42</jats:sub>-induced AD mouse model. Aβ<jats:sub>1 − 42</jats:sub> 5μL/5min/mouse was injected intracerebroventricularly (i.c.v.) into wild-type adult mice brain to induce AD-like neurotoxicity. For biochemical analysis, Western blotting and confocal microscopy were performed. Remarkably, intraperitoneal (i.p.) treatment of Trolox (30 mg/kg/mouse for 2 weeks) reduced the AD pathology by reducing the expression of Aβ, phosphorylated tau (p-tau), and β-site amyloid precursor protein cleaving enzyme1 (BACE1) in both cortex and hippocampus regions of mice brain. Furthermore, Trolox-treatment decreased neuroinflammation by inhibiting Toll-like receptor 4 (TLR4), phosphorylated nuclear factor-κB (pNF-κB) and interleukin-1β (IL-1β), and other inflammatory biomarkers of glial cells [ionized calcium-binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP)]. Moreover, Trolox reduced oxidative stress by enhancing the expression of nuclear factor erythroid-related factor 2 (NRF2) and heme oxygenase 1 (HO1). Similarly, Trolox-induced synaptic markers, including synaptosomal associated protein 23 (SNAP23), synaptophysin (SYN), and post-synaptic density protein 95 (PSD-95), and memory functions in AD mice. Our findings could provide a useful and novel strategy for investigating new medications to treat AD-associated neurodegenerative diseases.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"99 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260207","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":"The intricate interplay between microglia and adult neurogenesis in Alzheimer’s disease","authors":"Iris Früholz, Melanie Meyer-Luehmann","doi":"10.3389/fncel.2024.1456253","DOIUrl":"https://doi.org/10.3389/fncel.2024.1456253","url":null,"abstract":"Microglia, the resident immune cells of the central nervous system, play a crucial role in regulating adult neurogenesis and contribute significantly to the pathogenesis of Alzheimer’s disease (AD). Under physiological conditions, microglia support and modulate neurogenesis through the secretion of neurotrophic factors, phagocytosis of apoptotic cells, and synaptic pruning, thereby promoting the proliferation, differentiation, and survival of neural progenitor cells (NPCs). However, in AD, microglial function becomes dysregulated, leading to chronic neuroinflammation and impaired neurogenesis. This review explores the intricate interplay between microglia and adult neurogenesis in health and AD, synthesizing recent findings to provide a comprehensive overview of the current understanding of microglia-mediated regulation of adult neurogenesis. Furthermore, it highlights the potential of microglia-targeted therapies to modulate neurogenesis and offers insights into potential avenues for developing novel therapeutic interventions.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260206","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}
Arwa Kurabi, Kwang Pak, Eun Jung Lee, Allen F. Ryan
{"title":"Combinatorial protection of cochlear hair cells: not too little but not too much","authors":"Arwa Kurabi, Kwang Pak, Eun Jung Lee, Allen F. Ryan","doi":"10.3389/fncel.2024.1458720","DOIUrl":"https://doi.org/10.3389/fncel.2024.1458720","url":null,"abstract":"BackgroundA number of drugs are toxic to the cochlear sensory cells known as hair cells (HCs), resulting in hearing loss. Treatment with survival-promoting growth factors, antioxidants, and inhibitors of cell death pathways or proteinases have been shown to reduce HC damage in <jats:italic>in vivo</jats:italic> and/or <jats:italic>in vitro</jats:italic> animal models. Conversely, translation to humans has often been disappointing. This may be due to the complexity of intracellular damage processes. We hypothesized that combining treatments targeting different cellular processes would be more effective.MethodsUsing an <jats:italic>in vitro</jats:italic> model of gentamicin ototoxicity for murine cochlear hair cells, we screened all 56 possible combinations of inhibitors targeting five different cell damage mechanisms, plus the activator of one cell survival pathway, each of which have been shown to be singly effective in preventing HC loss in experimental studies. A high dose of gentamicin (200 μM) was used over three days in culture. All compounds were added at a dosage below that required for significant protection in the assay, and only this single dose was then employed. This was done so that we could more easily detect interactive, as opposed to additive, effects.ResultsIncreasing protection of hair cells was observed as combinations of compounds were increased from two to four factors, although not all combinations were equally protective. The optimal combination of four compounds consisted of an anti-oxidant, an apoptosis inhibitor, an autophagy inhibitor and a protective growth factor. Increasing the number of factors to five or six resulted in decreased protection.ConclusionThe results support the hypothesis that targeting multiple cellular damage or survival pathways provides more an effective hair cell protection approach. The results help to identify critical interactions among the cellular processes that operate in gentamicin ototoxicity. They also suggest that inhibiting too many biological processes impairs functions critical to HC survival, resulting in decreased protection.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"58 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260210","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":"Vasoactive intestinal peptide-expressing interneurons modulate the effect of behavioral state on cortical activity","authors":"Ehsan Sabri, Renata Batista-Brito","doi":"10.3389/fncel.2024.1465836","DOIUrl":"https://doi.org/10.3389/fncel.2024.1465836","url":null,"abstract":"Animals live in a complex and changing environment with various degrees of behavioral demands. Behavioral states affect the activity of cortical neurons and the dynamics of neuronal populations, however not much is known about the cortical circuitry behind the modulation of neuronal activity across behavioral states. Here we show that a class of GABAergic inhibitory interneurons that express vasoactive intestinal peptide-expressing interneurons (VIP), namely VIP interneurons, play a key role in the circuits involved in the modulation of cortical activity by behavioral state, as reflected in the mice facial motion. We show that inhibition of VIP interneurons reduces the correlated activity between the behavioral state of the animal and the spiking of individual neurons. We also show that VIP inhibition during the quiet state decreases the synchronous spiking of the neurons but increases delta power and phase locking of spiking to the delta-band activity. Taken together our data show that VIP interneurons modulate the behavioral state-dependency of cortical activity across different time scales.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"13 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142191390","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}
Valerio Barabino, Ilaria Donati della Lunga, Francesca Callegari, Letizia Cerutti, Fabio Poggio, Mariateresa Tedesco, Paolo Massobrio, Martina Brofiga
{"title":"Investigating the interplay between segregation and integration in developing cortical assemblies","authors":"Valerio Barabino, Ilaria Donati della Lunga, Francesca Callegari, Letizia Cerutti, Fabio Poggio, Mariateresa Tedesco, Paolo Massobrio, Martina Brofiga","doi":"10.3389/fncel.2024.1429329","DOIUrl":"https://doi.org/10.3389/fncel.2024.1429329","url":null,"abstract":"IntroductionThe human brain is an intricate structure composed of interconnected modular networks, whose organization is known to balance the principles of segregation and integration, enabling rapid information exchange and the generation of coherent brain states. Segregation involves the specialization of brain regions for specific tasks, while integration facilitates communication among these regions, allowing for efficient information flow. Several factors influence this balance, including maturation, aging, and the insurgence of neurological disorders like epilepsy, stroke, or cancer. To gain insights into information processing and connectivity recovery, we devised a controllable <jats:italic>in vitro</jats:italic> model to mimic and investigate the effects of different segregation and integration ratios over time.MethodsWe designed a cross-shaped polymeric mask to initially establish four independent sub-populations of cortical neurons and analyzed how the timing of its removal affected network development. We evaluated the morphological and functional features of the networks from 11 to 18 days <jats:italic>in vitro</jats:italic> (DIVs) with immunofluorescence techniques and micro-electrode arrays (MEAs).ResultsThe removal of the mask at different developmental stages of the network lead to strong variations in the degree of intercommunication among the four assemblies (altering the segregation/integration balance), impacting firing and bursting parameters. Early removal (after 5 DIVs) resulted in networks with a level of integration similar to homogeneous controls (without physical constraints). In contrast, late removal (after 15 DIVs) hindered the formation of strong inter-compartment connectivity, leading to more clustered and segregated assemblies.DiscussionA critical balance between segregation and integration was observed when the mask was removed at DIV 10, allowing for the formation of a strong connectivity among the still-separated compartments, thus demonstrating the existence of a time window in network development in which it is possible to achieve a balance between segregation and integration.","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"9 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142191387","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}