Frontiers in Neural Circuits最新文献

{"title":"Asymmetric neuromodulation in the respiratory network contributes to rhythm and pattern generation.","authors":"Rishi R Dhingra, Peter M MacFarlane, Peter J Thomas, Julian F R Paton, Mathias Dutschmann","doi":"10.3389/fncir.2025.1532401","DOIUrl":"https://doi.org/10.3389/fncir.2025.1532401","url":null,"abstract":"<p><p>Like other brain circuits, the brainstem respiratory network is continually modulated by neurotransmitters that activate slow metabotropic receptors. In many cases, activation of these receptors only subtly modulates the respiratory motor pattern. However, activation of some receptor types evokes the arrest of the respiratory motor pattern as can occur following the activation of μ-opioid receptors. We propose that the varied effects of neuromodulation on the respiratory motor pattern depend on the pattern of neuromodulator receptor expression and their influence on the excitability of their post-synaptic targets. Because a comprehensive characterization of these cellular properties across the respiratory network remains challenging, we test our hypothesis by combining computational modeling with ensemble electrophysiologic recording in the pre-Bötzinger complex (pre-BötC) using high-density multi-electrode arrays (MEA). Our computational model encapsulates the hypothesis that neuromodulatory transmission is organized asymmetrically across the respiratory network to promote rhythm and pattern generation. To test this hypothesis, we increased the strength of subsets of neuromodulatory connections in the model and used selective agonists <i>in situ</i> while monitoring pre-BötC ensemble activities. The <i>in silico</i> simulations of increasing slow inhibition were consistent with experiments examining the effect of systemic administration of the 5HT1aR agonist 8-OH-DPAT. Similarly, the effects of increasing slow excitation in the model were experimentally confirmed in pre-BötC ensemble activities before and after systemic administration of the <i>μ</i>-opioid receptor agonist fentanyl. We conclude that asymmetric neuromodulation can contribute to respiratory rhythm and pattern generation and accounts for its varied effects on breathing.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1532401"},"PeriodicalIF":3.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689853","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":"Neonatal testosterone exposure alleviates female-specific severity of formalin-induced inflammatory pain in mice.","authors":"Moeko Kanaya, Yoshifumi Ueta, Makiko Mochizuki-Kashio, Ayako Nakamura-Ishizu, Mariko Miyata","doi":"10.3389/fncir.2025.1593443","DOIUrl":"10.3389/fncir.2025.1593443","url":null,"abstract":"<p><p>Gonadal hormones may influence higher pain sensitivity in females than males by transiently activating the central pain pathway and organizing sexually dimorphic neuronal circuits during development. The latter effects of gonadal hormones, called organizational effects, are critical for establishing sex-specific reproductive functions and transforming them postnatally. However, it remains unclear whether the organizational effects determine sex-specific pain severity in adulthood. In this study, testosterone administration to female mice on day of birth alleviated intraplantar formalin injection-induced inflammatory pain in adulthood, resulting in comparable severity to males. In contrast, intense pain persisted in females with adult testosterone administration. We found no sex differences in thermal pain responses and spinal reflexes. Formalin injection similarly increased c-Fos activity in the spinal dorsal horn in both sexes, suggesting the involvement of supraspinal mechanisms and/or immune responses in sex-specific inflammatory pain. In the periaqueductal gray (PAG) region related to the descending pain modulation pathway, formalin increased c-Fos-positive cells in the lateral region of males but not females. In the bed nucleus of the stria terminalis (BNST) related to affective pain responses, formalin increased c-Fos-positive cells in females. Notably, in common with these regions, testosterone administration to neonatal females changed formalin-induced c-Fos activity from the female to the male type. We further examined the involvement of immune cells. Systemic microglial ablation using PLX3397 suppressed formalin-induced pain in a sex-independent manner. Although formalin injection changed T lymphocyte subsets in the peripheral blood in females, it was independent from neonatal testosterone administration. Therefore, the organizational effects of testosterone determine the male characteristic of formalin-induced inflammatory pain, possibly via sexually dimorphic PAG and BNST functions.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1593443"},"PeriodicalIF":3.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649044","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":"Neural control meets biomechanics in the motor assessment of neurological disorders: a narrative review.","authors":"Mirjam Bonanno, Paolo De Pasquale, Bartolo Fonti, Elvira Gjonaj, Simona De Salvo, Angelo Quartarone, Rocco Salvatore Calabrò","doi":"10.3389/fncir.2025.1608328","DOIUrl":"10.3389/fncir.2025.1608328","url":null,"abstract":"<p><p>The emerging concept of \"neurobiomechanics\" embodies an integrative approach, bringing together insights from functional anatomy, the physiology of the musculoskeletal and central nervous systems, physics, and computer science. By examining human movement under normal, optimal, and pathological conditions, neurobiomechanics aims to unravel the intricate mechanisms driving motor function and dysfunction, offering a comprehensive perspective on disorders such as acquired brain injury and neurodegenerative diseases. In this narrative review, we sought to explore the \"neurobiomechanics\" as a potential approach to investigate both neural and biomechanical aspects of human motion, trying to answer the following questions: (1) \"Which technologies can perform a neurobiomechanical assessment in neurological patients?,\" (2) \"What are the key neurophysiological and biomechanical parameters?,\" (3) \"How can we translate this approach from research to clinical practice?.\" We have found that, to assess/understand a patient's dysfunctional patterns, it is necessary to evaluate both neurophysiology and biomechanics in a complementary manner. In other words, assessing one aspect without the other is not sufficient, as this may lead to incomplete evaluations from both a functional and methodological perspective.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1608328"},"PeriodicalIF":3.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12245779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625925","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":"Dissociated neuronal cultures as model systems for self-organized prediction.","authors":"Amit Yaron, Zhuo Zhang, Dai Akita, Tomoyo Isoguchi Shiramatsu, Zenas C Chao, Hirokazu Takahashi","doi":"10.3389/fncir.2025.1568652","DOIUrl":"10.3389/fncir.2025.1568652","url":null,"abstract":"<p><p>Dissociated neuronal cultures provide a powerful, simplified model for investigating self-organized prediction and information processing in neural networks. This review synthesizes and critically examines research demonstrating their fundamental computational abilities, including predictive coding, adaptive learning, goal-directed behavior, and deviance detection. A unique contribution of this work is the integration of findings on network self-organization, such as the development of critical dynamics optimized for information processing, with emergent predictive capabilities, the mechanisms of learning and memory, and the relevance of the free energy principle within these systems. Building on this, we discuss how insights from these cultures inform the design of neuromorphic and reservoir computing architectures, aiming to enhance energy efficiency and adaptive functionality in artificial intelligence. Finally, this review outlines promising future directions, including advancements in three-dimensional cultures, multi-compartment models, and brain organoids, to deepen our understanding of hierarchical predictive processes in both biological and artificial systems, thereby paving the way for novel, biologically inspired computing solutions.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1568652"},"PeriodicalIF":3.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600002","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":"Research progress on the neural circuits mechanisms of anxiety.","authors":"Wenxuan Gong","doi":"10.3389/fncir.2025.1609145","DOIUrl":"10.3389/fncir.2025.1609145","url":null,"abstract":"<p><p>Anxiety disorders, as a critical mental health issue, profoundly impact an individual's quality of life and social participation while imposing a considerable economic burden on communities. This underlines the urgent need for in-depth studies on the mechanisms underlying anxiety-like behaviors. These mechanisms are overseen by intricate neural regulatory networks, and the understanding of them has significantly advanced in recent decades, largely due to breakthroughs in neuroscience. Traditionally, research on brain regions controlling anxiety responses has been focused on key brain regions. However, recent studies have expanded this scope to encompass a broader network, including the amygdala, the bed nucleus of the stria terminalis (BNST), and the lateral habenula (LHb). Each of these regions plays a distinct role in mediating specific components of anxiety-like behaviors: the amygdala is central to emotional processing, the BNST contributes to the prolonged state of anxiety, and the LHb is pivotal in encoding negative signals that amplify aversive emotions. This review underscores the evolving and interconnected nature of these neural circuits, illustrating the intricate interplay in shaping anxiety-like behaviors. By proposing a layered representation of the neural circuitry, this study aims to unravel the neurobiological basis of anxiety-like behaviors, paving the way for more effective therapeutic strategies. These insights hold promise for advancing treatment approaches that could alleviate the burden of anxiety disorders in the future.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1609145"},"PeriodicalIF":3.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600003","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":"How early olfactory experiences influence brain development in mice.","authors":"Hirofumi Nishizumi","doi":"10.3389/fncir.2025.1608270","DOIUrl":"10.3389/fncir.2025.1608270","url":null,"abstract":"<p><p>Mammalian sensory systems develop through both activity-dependent and activity-independent processes. While the foundational neural circuits are encoded by genetics, their refinement depends on activity-driven mechanisms. During the neonatal critical period - a specific developmental phase - sensory circuits adapt and mature in response to environmental stimuli. Initially, this plasticity is reversible, but over time, it becomes permanent. Lack of adequate stimulation during this phase can lead to impaired neural function, highlighting the importance of sensory input for optimal system development. In mice, olfactory neural circuits are first established largely through genetic programming. However, early exposure to environmental odors is crucial in shaping these circuits, affecting both odor perception and social behaviors. This review explores recent findings on the development of olfactory circuits in mice and their impact on behavior.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1608270"},"PeriodicalIF":3.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483790","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":"<i>Otx2</i> mRNA expression is downregulated following traumatic brain injury in zebra finches.","authors":"Adam Talwalkar, Kelli A Duncan","doi":"10.3389/fncir.2025.1591983","DOIUrl":"10.3389/fncir.2025.1591983","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) induces a wide range of neurodegenerative symptoms, yet effective treatment strategies remain limited. Emerging evidence suggests that post-TBI recovery recapitulates aspects of early brain development, highlighting the potential for developmental molecular mechanisms to inform therapeutic interventions. The transcription factor <i>Otx2</i> is critical for early brain and sensory organ development, as well as the maintenance of retinal and neural function in adulthood. Notably, the transfer of <i>Otx2</i> homeoprotein into parvalbumin-expressing (PV+) GABAergic interneurons is essential for opening and closing critical periods of plasticity across vertebrates. Here, we investigate the acute regulation of <i>Otx2</i> mRNA following TBI in adult zebra finches (ZF) to evaluate its potential as a target for future study and therapeutic manipulation in neural repair. Adult ZFs sustained unilateral hemispheric brain injuries, and qPCR was used to quantify <i>Otx2</i> mRNA expression at 24 hours and 1 week post-injury in both males and females. Our findings reveal a significant downregulation of <i>Otx2</i> mRNA expression following injury, highlighting <i>Otx2</i> as a potential target for further investigation and manipulation. These results provide insight into the molecular response to brain injury and suggest a potential link between developmental pathways and post-injury plasticity.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1591983"},"PeriodicalIF":3.4,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474654","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":"Facial affect and arousal as a complement to gaze measures in infant speech sound perception studies.","authors":"Sho Tsuji, Fernanda Alonso, Hiromichi Hagihara, Nanako Kimura, Linda Polka, Irena Lovčević","doi":"10.3389/fncir.2025.1553918","DOIUrl":"10.3389/fncir.2025.1553918","url":null,"abstract":"<p><p>This study explores infant facial expressions during visual habituation to investigate perceptual attunement to native and non-native speech sounds. Using automated facial affect analysis based on Facial Action Units, we analyzed valence, arousal, positive affect, and negative affect during the experiment. Valence and arousal decreased with habituation, while positive affect increased, with differences between native and non-native stimuli. Facial affect showed links to discrimination outcomes, with better native discrimination linked to reduced negative affect. These findings highlight the potential of facial expression analysis as a complementary tool to gaze-based measures in early language development research.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1553918"},"PeriodicalIF":3.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301690","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":"The striatal compartments, striosome and matrix, are embedded in largely distinct resting-state functional networks.","authors":"Alishba Sadiq, Adrian T Funk, Jeff L Waugh","doi":"10.3389/fncir.2025.1514937","DOIUrl":"10.3389/fncir.2025.1514937","url":null,"abstract":"<p><p>The striatum is divided into two interdigitated tissue compartments, the striosome and matrix. These compartments exhibit distinct anatomical, neurochemical, and pharmacological characteristics and have separable roles in motor and mood functions. Little is known about the functions of these compartments in humans. While compartment-specific roles in neuropsychiatric diseases have been hypothesized, they have yet to be directly tested. Investigating compartment-specific functions is crucial for understanding the symptoms produced by striatal injury, and to elucidating the roles of each compartment in healthy human skills and behaviors. We mapped the functional networks of striosome-like and matrix-like voxels in humans <i>in-vivo</i>. We utilized a diverse cohort of 674 healthy adults, derived from the Human Connectome Project, including all subjects with complete diffusion and functional MRI data and excluding subjects with substance use disorders. We identified striatal voxels with striosome-like and matrix-like structural connectivity using probabilistic diffusion tractography. We then investigated resting-state functional connectivity (rsFC) using these compartment-like voxels as seeds. We found widespread differences in rsFC between striosome-like and matrix-like seeds (<i>p</i> < 0.05, family wise error corrected for multiple comparisons), suggesting that striosome and matrix occupy distinct functional networks. Slightly shifting seed voxel locations (<4 mm) eliminated these rsFC differences, underscoring the anatomic precision of these networks. Striosome-seeded networks exhibited ipsilateral dominance; matrix-seeded networks had contralateral dominance. Next, we assessed compartment-specific engagement with the triple-network model (default mode, salience, and frontoparietal networks). Striosome-like voxels dominated rsFC with the default mode network bilaterally. The anterior insula (a primary node in the salience network) had higher rsFC with striosome-like voxels. The inferior and middle frontal cortices (primary nodes, frontoparietal network) had stronger rsFC with matrix-like voxels on the left, and striosome-like voxels on the right. Since striosome-like and matrix-like voxels occupy highly segregated rsFC networks, striosome-selective injury may produce different motor, cognitive, and behavioral symptoms than matrix-selective injury. Moreover, compartment-specific rsFC abnormalities may be identifiable before disease-related structural injuries are evident. Localizing rsFC differences provides an anatomic substrate for understanding how the tissue-level organization of the striatum underpins complex brain networks, and how compartment-specific injury may contribute to the symptoms of specific neuropsychiatric disorders.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1514937"},"PeriodicalIF":3.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198807","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":"Disrupted functional connectome in a rodent model of autism during social isolation.","authors":"Robert Gergely Kemecsei, Szizel Dániel-Papp, David Barnabas Balazs, Estifanos Ghebrihiwet Tewelde, Andras Csillag, Gergely Zachar","doi":"10.3389/fncir.2025.1525130","DOIUrl":"10.3389/fncir.2025.1525130","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is associated with disruptions in social behavior and the neural circuitry behind it. Very little data is available on the mechanisms that are responsible for the lack of motivation to reunite with conspecifics during isolation. It is as important to investigate the neural changes that reduce motivation to end social isolation, as those underlying the reactions to social stimuli. Using a rodent model of prenatal valproic acid (VPA) exposure, we investigated how social isolation affects the neural activation of key brain nuclei involved in social processing and stress regulation. Juvenile male C57BL/6 mice were treated prenatally with VPA or saline (CTR) and subjected to 24 h of social isolation from their cage mates, with neural activity assessed via c-Fos immunohistochemistry. Based on correlational activations we reconstructed and analyzed the functional connectome of the observed brain regions. Control animals exhibited elevated c-Fos expression in the regions central to the mesolimbic reward system (MRS), social brain network (SBN), and stress-related networks, with the interpeduncular nucleus (IPN) at the core, compared to VPA-treated animals. Functional network analysis revealed a more widespread but less specific pattern of connectivity in VPA-treated animals. These findings suggest that prenatal VPA exposure disrupts certain neural circuits related to social behavior and stress regulation, offering an insight into the altered perception of social isolation in ASD models, and highlighting potential therapeutic targets.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1525130"},"PeriodicalIF":3.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173468","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}