Frontiers in Cellular Neuroscience最新文献

{"title":"Mu-opioid and nociceptin receptors show divergent, cell-type-specific actions in the mesocorticolimbic reward system in opioid use disorder.","authors":"Marie-Charlotte Allichon, Jeanne Espinosa, Rebecca H Cole, Mei-Chuan Ko, Peter Vanhoutte, Max E Joffe","doi":"10.3389/fncel.2026.1774384","DOIUrl":"https://doi.org/10.3389/fncel.2026.1774384","url":null,"abstract":"<p><p>The mu-opioid receptor (MOR) and the nociceptin/orphanin FQ receptor (NOPR) are closely related yet functionally distinct modulators of rewards, motivation, and affect. Within the mesocorticolimbic system, including the prefrontal cortex (PFC), the ventral tegmental area (VTA) and the nucleus accumbens (NAc), these receptors exhibit divergent, cell type-specific expression patterns that drive opposing behavioral outcomes. For example, MOR activation enhances rewards processing and reinforcement by facilitating dopamine transmission, whereas NOPR signaling in the VTA can reduce dopamine cell activity. In addition, MOR and NOPR are positioned within cortical circuits to preferentially reduce GABA and glutamate transmission, respectively. This review synthesizes current knowledge on how MOR and NOPR coordinate motivational and affective states through distinct neuronal populations across the mesocorticolimbic circuit. We also discuss emerging evidence for functional interactions between these systems and the therapeutic implications of pharmacological strategies targeting both receptors, including dual-acting MOR/NOPR ligands that enhance analgesic efficacy with reduced abuse liability. By integrating behavioral, molecular, and circuit-level findings, this synthesis aims to clarify how MOR and NOPR signaling jointly shape rewards and stress pathways, and provide insight into the development of safer and more effective treatments for opioid use disorders.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1774384"},"PeriodicalIF":4.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13106015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767162","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":"Yellow cerebrospinal fluid in an extremely preterm infant: a case report.","authors":"Xiyang Chen, Haiting Li, Jie Li, Linlin Chen, Xixi Liu, Dengpan Xie, Yunqin Chen, Junhui Yuan, Enfu Tao","doi":"10.3389/fncel.2026.1792995","DOIUrl":"https://doi.org/10.3389/fncel.2026.1792995","url":null,"abstract":"<p><p>Although phototherapy has reduced the incidence of kernicterus in term infants, it remains a significant threat to extremely preterm infants due to their immature blood-brain barrier and frequent comorbidities such as sepsis. Current clinical practice relies on serum total bilirubin levels, which may not accurately reflect cerebral bilirubin exposure in this vulnerable population. This case report describes an extremely preterm infant (gestational age 28 1/7 weeks, birth weight 950 g) who developed visibly yellow cerebrospinal fluid (CSF) on the first day of life. Despite only minimal serum hyperbilirubinemia (4.4 mg/dL; ≈ 75.2 μmol/L), CSF bilirubin was markedly elevated at 10 mg/dL (≈ 171 μmol/L). The infant presented with respiratory distress syndrome and sepsis. Immediate intensive phototherapy was initiated, leading to the normalization of CSF bilirubin (3.6 mg/dL ≈ 61.5 μmol/L) within 4 days. Brain magnetic resonance imaging (MRI) and automated auditory brainstem response (AABR) performed at the corrected age of 4 months were both unremarkable. At the corrected age of 12 months, neurodevelopmental assessment using the Bayley Scales of Infant Development-III (BSID-III) showed scores within the normal range. This case illustrates that CSF bilirubin can serve as a sensitive early biomarker for identifying preterm infants at imminent risk for bilirubin neurotoxicity, particularly when serum bilirubin levels are misleadingly low. Targeted measurement of CSF bilirubin in selected high-risk infants, when a lumbar puncture is otherwise indicated, could enable more timely intervention and contribute to improved neurodevelopmental outcomes.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1792995"},"PeriodicalIF":4.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767249","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":"Intestinal inflammation promotes neuroinflammation and PD-associated nigrostriatal pathology independently of LRRK2 G2019S kinase activity.","authors":"Andrea R Merchak, Mary K Herrick, Madelyn C Houser, Cody E Keating, Jianjun Chang, Malú Gámez Tansey","doi":"10.3389/fncel.2026.1794784","DOIUrl":"https://doi.org/10.3389/fncel.2026.1794784","url":null,"abstract":"<p><strong>Introduction: </strong>The pathogenesis of Parkinson's disease (PD) has been linked to environmental factors, toxins, genetics, and peripheral inflammation. Importantly, intestinal inflammation like that seen in Crohn's disease (CD) or food allergies has been implicated in risk for neurodegeneration and late-onset PD. Further, CD and PD share genetic risk factors including gain-of-function leucine-rich repeat kinase 2 (<i>LRRK2</i>) mutations. Here, we aim to better understand how intestinal inflammation synergizes with <i>Lrrk2</i> levels or kinase activation to promote neurodegeneration in young and old mice.</p><p><strong>Methods: </strong>We utilized bacterial artificial chromosome (BAC) mice overexpressing wildtype mouse <i>Lrrk2</i> or mutant G2019S mouse <i>Lrrk2</i> and compared them with C57B6J mice at baseline and under conditions of intestinal inflammation using dextran sodium sulfate (DSS) colitis models.</p><p><strong>Results: </strong>While our data revealed regulation of the brain inflammatory state by <i>Lrrk2</i>, we did not observe age-dependent selective vulnerability or protection in <i>Lrrk2</i> mouse lines in colitis protocols. Instead, DSS phenotypes were associated with increased nigrostriatal dysregulation in all genotypes independent of age.</p><p><strong>Discussion: </strong>While <i>Lrrk2</i> mutations appear to influence the genesis of peripheral inflammation, our data suggest that <i>Lrrk2</i> activation due to a gain-of-function mutation does not exacerbate the effects of inflammation on nigrostriatal degeneration in this model.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1794784"},"PeriodicalIF":4.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767184","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":"Presynaptic chloride-dependent regulation of spontaneous glutamate release in the rat medial preoptic nucleus.","authors":"Mario Pérez-Del-Pozo, Tatiana Kuznetsova, Staffan Johansson, Michael Druzin","doi":"10.3389/fncel.2026.1800250","DOIUrl":"https://doi.org/10.3389/fncel.2026.1800250","url":null,"abstract":"<p><p>Neurosteroids and inhibitory neurotransmitters can modulate neurotransmitter release from presynaptic terminals, yet the mechanisms underlying such modulation remain unclear. In this study, we investigated how presynaptic glycine and GABA_AR-receptors (GlyRs and GABA_ARs) regulate glutamate release onto neurons in the medial preoptic nucleus (MPN), a hypothalamic region critically involved in reproductive and social behaviors. Using patch-clamp recordings from mechanically dissociated MPN neurons with functionally preserved presynaptic terminals, we selectively examined local presynaptic effects of receptor activation. Both the neurosteroid allopregnanolone and the selective GABA_AR agonist muscimol consistently increased the frequency of glutamate-mediated spontaneous excitatory postsynaptic currents (sEPSCs). This facilitation was sensitive to the GABA_AR-blocker picrotoxin, abolished by inhibition of sodium-potassium-chloride cotransporter 1 (NKCC1) or by the sodium-channel blocker tetrodotoxin, consistent with a mechanism involving depolarizing chloride efflux driven by a high intraterminal chloride ion concentration and subsequent sodium-dependent recruitment of presynaptic calcium channels. In contrast, activation of presynaptic GlyRs produced bidirectional effects on glutamate release: facilitation in some terminals and inhibition in others. We demonstrate that the inhibitory effect likely depends on low intraterminal chloride concentration maintained by the potassium-chloride cotransporter 2 (KCC2), which enables chloride influx and hyperpolarization upon GlyR activation. Consistent with this mechanism, pharmacological blockade of chloride extrusion abolished glycine-induced inhibition, and immunogold labeling revealed KCC2 presence in a subset of presynaptic terminals innervating MPN neurons. Together, these findings suggest functional presynaptic KCC2 in central neurons and identify presynaptic chloride homeostasis as a key determinant of synapse-specific modulation of glutamate release in the MPN.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1800250"},"PeriodicalIF":4.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767238","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":"Microglial PD-1/PD-L1 axis in CNS demyelinating diseases: a dual immunoregulatory perspective.","authors":"Meiling Zhou, Xiying Yao, Lingchun Liu, Yuan Gao, Wenli Chen, Kunwen Zheng, Haixia Li, Qiang Meng","doi":"10.3389/fncel.2026.1815351","DOIUrl":"https://doi.org/10.3389/fncel.2026.1815351","url":null,"abstract":"<p><p>Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) stand as archetypal autoimmune-mediated demyelinating diseases of the central nervous system (CNS). Emerging evidence highlights the dual immunomodulatory functions of microglia in these diseases: on the one hand, they can secrete neurotoxic molecules that exacerbate neural damage; on the other hand, they are capable of releasing neuroprotective factors that promote tissue repair and enhance neuronal survival. This review dissects the programmed cell death ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) immune checkpoint axis, expressed on activated microglia, T cells, and other immune cells, as a pivotal rheostat of neuroinflammation. The binding of PD-1 to PD-L1 dampens immune cell activation and proliferation, curtails pro-inflammatory cytokine output, and is instrumental in preserving immune tolerance. In the context of chronic inflammation, persistent PD-1/PD-L1 signaling has been closely associated with the induction of T cell exhaustion than with direct apoptosis, though context-dependent effects on cell survival have been reported in certain experimental paradigms. Both microglia and the PD-1/PD-L1 axis are critically intertwined in the initiation and perpetuation of CNS demyelinating diseases. A more granular comprehension of their interplay will not only illuminate the molecular underpinnings of neuroinflammation and immune regulation in MS and NMOSD but also pave the way for crafting precision immunotherapies aimed at modulating microglial polarization. Here, we systematically review the dual immunomodulatory functions of the microglial PD-1/PD-L1 axis in these diseases and deliberate on the therapeutic prospects of targeting this pathway, thereby furnishing a conceptual framework for novel immune intervention strategies.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1815351"},"PeriodicalIF":4.0,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13099302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767181","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":"Deletion of <i>Cacna1c</i> (Ca _<i>V</i> 1.2) in D1-expressing cells elicits divergent sex-specific effects on aversive and spatial memories.","authors":"Josiah D Walsh, Diego Scala-Chavez, Andrew S Lee, Arlene Martínez-Rivera, Anjali M Rajadhyaksha","doi":"10.3389/fncel.2026.1776165","DOIUrl":"https://doi.org/10.3389/fncel.2026.1776165","url":null,"abstract":"<p><p>Dopamine signaling is critical for cognitive and emotional regulation and is implicated in multiple neuropsychiatric disorders. One downstream effector of dopamine is the L-type calcium channel CaV1.2, encoded by the risk gene <i>CACNA1C</i>. Genome-wide association studies have consistently linked <i>CACNA1C</i> single nucleotide polymorphisms to schizophrenia, bipolar disorder, and related conditions. We previously showed that homozygous deletion of <i>Cacna1c</i> in dopamine receptor 1 (D1)-expressing cells enhances remote (30 days post-training) contextual fear memory in male mice. Here, we extend these findings by examining sex- and gene dosage-dependent behavioral consequences of <i>Cacna1c</i> loss in D1 cells. We find a sex-dependent dissociation, where females show enhanced aversive memory up to 30 days post-training even with partial <i>Cacna1c</i> loss, whereas males require complete loss to show enhanced fear. In contrast, males show impaired spatial memory in the Water Y-maze following heterozygous or homozygous deletion, an effect not observed in females. Cue-associated fear memory was transiently elevated in females but unaffected in males. Locomotor activity was reduced in females during the initial minutes of testing, with no effects in males, while social interaction and anxiety-like behaviors were unchanged across groups. These findings indicate that Ca _<i>v</i> 1.2 signaling in D1-expressing cells differentially regulates aversive versus spatial memory in a sex-dependent manner, providing insight into how <i>CACNA1C</i> risk variants may contribute to sex-specific cognitive phenotype.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1776165"},"PeriodicalIF":4.0,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13099333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767208","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":"Correction: Discovery and optimization of tau targeted protein degraders enabled by patient induced pluripotent stem cells-derived neuronal models of tauopathy.","authors":"M Catarina Silva, Ghata Nandi, Katherine A Donovan, Quan Cai, Bethany C Berry, Radoslaw P Nowak, Eric S Fischer, Nathanael S Gray, Fleur M Ferguson, Stephen J Haggarty","doi":"10.3389/fncel.2026.1830139","DOIUrl":"https://doi.org/10.3389/fncel.2026.1830139","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fncel.2022.801179.].</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1830139"},"PeriodicalIF":4.0,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13097065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767228","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":"Neuronal differentiation and activity drive nucleocytoplasmic shuttling of the intellectual disability kinase TLK2.","authors":"Lubna Nuhu-Soso, Heidi Denton, Darren L Goffin, Ines Hahn, Gareth J O Evans","doi":"10.3389/fncel.2026.1699735","DOIUrl":"https://doi.org/10.3389/fncel.2026.1699735","url":null,"abstract":"<p><strong>Introduction: </strong>Autosomal dominant intellectual developmental disorder 57 (MRD57) is a rare neurodevelopmental disorder characterised by delayed language and psychomotor development, intellectual disability, hypotonia, gastrointestinal issues and facial dysmorphia. It is linked to genetic mutations in the serine/threonine kinase TLK2, which generally cause haploinsufficiency. TLK2 is an established cell cycle regulator that has been extensively studied in mitotic cells. It is upregulated in cancers, driving tumour growth, however, the role of TLK2 in postmitotic neurons is not understood. We therefore aimed to determine where TLK2 is expressed in the brain and its subcellular localisation during neuronal differentiation.</p><p><strong>Methods: </strong>We analysed TLK2 transcript or protein expression and localisation in public RNAseq datasets, mouse brain sections, and a rat neuroblastoma cell line model of neuronal differentiation.</p><p><strong>Results: </strong>Human and mouse brain transcriptomic data revealed splice variant diversity in the N-terminus of TLK2, which contains its nuclear localisation sequence (NLS). Using splice-specific in situ hybridisation probes, we observed expression of TLK2 transcripts that contain and lack the NLS in the mouse hippocampus and cerebellum. Surprisingly, TLK2 protein was predominantly cytoplasmic in the adult mouse brain. Similarly, in rat neuroblastoma cells, we found that neuronal differentiation enhances a cytoplasmic pool of TLK2 by two mechanisms: nuclear export of full length TLK2 and increased expression of TLK2 splice variants lacking the NLS. Finally, acute stimuli that mimic synaptic activity were sufficient to elicit nuclear export of TLK2.</p><p><strong>Discussion: </strong>Our data highlight a previously unrecognised role of cytoplasmic TLK2 in neurons and future studies should determine how the loss of TLK2 activity in MRD57 impacts cytoplasmic TLK2 substrates in the developing and mature brain.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1699735"},"PeriodicalIF":4.0,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13095609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767231","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":"From mice to clinical relevance: humanizing neuroscience with human-based model systems.","authors":"Aniella Vanessa Bak, Karen M J van Loo, Deborah Kronenberg-Versteeg, Henner Koch","doi":"10.3389/fncel.2026.1776439","DOIUrl":"10.3389/fncel.2026.1776439","url":null,"abstract":"<p><p>Preclinical research in neuroscience has traditionally relied on animal models to investigate disease mechanisms and develop new therapeutic strategies. While these models are valuable to gain mechanistic insights, their translational power remains limited due to interspecific differences and, hence, frequent failures in clinical translation. The uniqueness of the human brain calls for alternative approaches in neuroscientific research that more faithfully capture human physiology and pathology. In recent years, a variety of human-based model systems have emerged, ranging from dissociated neuronal cultures and stem cell-derived platforms, including organoids, to micro-engineered devices and human brain slice approaches. Each model offers distinct advantages and limitations in recapitulating neural circuits, disease mechanisms, and therapeutic responses. In this review, we critically discuss the merits and drawbacks of animal models, outline the historic development and current applications of human-based systems, and highlight their potential to complement or replace animal-based models. We further explore current challenges in human brain research, including human variability, technical challenges, as well as ethical considerations and regulatory hurdles. Together, these advances represent a shift toward more predictive, human, and ethically responsible neuroscientific research that could aid in decreasing the translational gap.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1776439"},"PeriodicalIF":4.0,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13083016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722154","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":"Utilizing a culture system for horizontal cells to study neural circuit assembly in the developing mouse retina.","authors":"Ross M Perez, Yong H Park, Ajeet Singh, Collin Todora, Marlon F Mattos, Daniela Becerril, Rajashree Venkatraman, Arlene A Hirano, Nicholas C Brecha, Rinki Ratnapriya, Benjamin J Frankfort, Elizabeth Zuniga-Sanchez","doi":"10.3389/fncel.2026.1691122","DOIUrl":"https://doi.org/10.3389/fncel.2026.1691122","url":null,"abstract":"<p><p>The precise wiring of the nervous system relies on neurons extending their processes at the right time and place to find their appropriate synaptic partner. The mechanisms that determine when and where neurons extend their neurites during synaptogenesis remains a central question in the field. In the present study, we used a cell culture system coupled with live imaging to investigate the wiring mechanisms in the developing mouse retina. We focused on horizontal cells which are a class of interneurons in the outer mouse retina known to synapse selectively to the distinct types of photoreceptors. Previous research has shown horizontal cells extend their neurites and make connections to their respective photoreceptor partner in a temporal- and spatial-dependent manner. However, the mechanisms responsible for their selective wiring to photoreceptors during development remains poorly understood. To answer this question, we developed a horizontal cell culture system to investigate the cellular mechanisms responsible for neurite outgrowth during circuit assembly. Our data shows cultured horizontal cells extend neurites with a similar morphology as <i>in vivo</i>. Moreover, neurite extension of horizontal cells is limited to early developmental stages as young mice extend more complex processes compared to those from adolescent retinas. We also found that horizontal cells, unlike retinal ganglion cells, do not extend neurites when cultured alone and require other retinal neurons to promote neurite outgrowth. In summary, we established a horizontal cell culture system that can be used to decipher the mechanisms involved in neural circuit assembly of the mouse retina.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"20 ","pages":"1691122"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698005","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}