Frontiers in Neural Circuits最新文献

{"title":"NMDA receptor antagonist induced c-Fos expression in the medial entorhinal cortex during postnatal development.","authors":"Feng Liang, Hong Wang, Robert Konrad Naumann","doi":"10.3389/fncir.2025.1619534","DOIUrl":"10.3389/fncir.2025.1619534","url":null,"abstract":"<p><p><i>N</i>-methyl-D-aspartate receptor (NMDAR) antagonists, including ketamine, phencyclidine (PCP), and dizocilpine (MK-801), are an important class of drugs that can produce antidepressant, hallucinogenic, dissociative, psychotomimetic, and anesthetic effects in humans and animal models. To understand the effects of NMDAR antagonists on the brain, it is essential to map their actions at cellular resolution. We quantified c-Fos expressing cells in the mouse telencephalon after systemic injection of the potent NMDAR antagonist MK-801 and found a 10-fold higher density of c-Fos in the medial entorhinal cortex (MEC) compared to other regions of the telencephalon. c-Fos density was high in layer 3 of the dorsal MEC but low in other parts of the MEC. Since previous studies have shown that parvalbumin (PV) staining shows a strong dorsal-ventral gradient in the MEC, we investigated the spatial correlation between c-Fos and PV staining. We classified PV neurons based on their level of immunoreactivity and found that high and medium PV neurons were positively correlated with c-Fos density, while low PV neurons were negatively correlated. To understand the temporal correlation of c-Fos and PV staining, we examined their expression patterns after MK-801 injections during postnatal development. PV expression emerged on postnatal day 12, preceding c-Fos expression, which emerged on postnatal day 16. Our results suggest that local circuits comprising specific subtypes of inhibitory and excitatory neurons are critical for generating a sustained neuronal response to NMDAR antagonists. Furthermore, a high density of PV neuron input may be a prerequisite for the induction of c-Fos expression observed in MEC principal neurons. This study contributes to our understanding of how the brain responds to NMDAR antagonists in the developing and adult brain and reveals cell types in the dorsal MEC that are highly sensitive to this class of drugs.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1619534"},"PeriodicalIF":3.0,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12339504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834813","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":"Vagus nerve stimulation modulates information representation of sustained activity in layer specific manner in the rat auditory cortex.","authors":"Tomoyo Isoguchi Shiramatsu, Kenji Ibayashi, Kensuke Kawai, Hirokazu Takahashi","doi":"10.3389/fncir.2025.1569158","DOIUrl":"10.3389/fncir.2025.1569158","url":null,"abstract":"<p><p>Understanding how vagus nerve stimulation (VNS) modulates cortical information processing is essential to developing sustainable, adaptive artificial intelligence inspired by biological systems. This study presents the first evidence that VNS alters the representation of auditory information in a manner that is both layer- and frequency band-specific within the rat auditory cortex. Using a microelectrode array, we meticulously mapped the band-specific power and phase-locking value of sustained activities in layers 2/3, 4, and 5/6, of the rat auditory cortex. We used sparse logistic regression to decode the test frequency from these neural characteristics and compared the decoding accuracy before and after applying VNS. Our results showed that VNS impairs high-gamma band representation in deeper layers (layers 5/6), enhances theta band representation in those layers, and slightly improves high-gamma representation in superficial layers (layers 2/3 and 4), demonstrating the layer-specific and frequency band-specific effect of VNS. These findings suggest that VNS modulates the balance between feed-forward and feed-back pathways in the auditory cortex, providing novel insights into the mechanisms of neuromodulation and its potential applications in brain-inspired computing and therapeutic interventions.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1569158"},"PeriodicalIF":3.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12325384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794010","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":"Bayesian estimation of orientation and direction tuning captures parameter uncertainty.","authors":"Zongting Wu, Stephen D Van Hooser","doi":"10.3389/fncir.2025.1542332","DOIUrl":"10.3389/fncir.2025.1542332","url":null,"abstract":"<p><p>This study explores the efficacy of Bayesian estimation in modeling the orientation and direction selectivity of neurons in the primary visual cortex (V1). Unlike traditional methods such as least squares, Bayesian estimation adeptly handles the probabilistic nature of neuronal responses, offering robust analysis even with limited data and weak selectivity. Through the analysis of both simulated and experimental data, we demonstrate that Bayesian estimation not only accurately fits the neuronal tuning curves but also effectively captures parameter certainty or uncertainty of both strongly and weakly selective neurons. Our results affirm the complex interdependencies among response parameters and highlight the variability in neuronal behavior under varied stimulus conditions. Our findings provide guidance as to how many response samples are necessary for Bayesian parameter estimation to achieve reliable fitting, making it particularly suitable for studies with constraints on data availability.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1542332"},"PeriodicalIF":3.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12319010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783973","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":"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":"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":3.0,"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":3.0,"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":3.0,"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 D 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":2.9,"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":3.0,"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":3.0,"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":3.0,"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}