Frontiers in Neural Circuits最新文献

{"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":"https://doi.org/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}

{"title":"Long-term self-reported symptoms and psychophysical tests in COVID-19 subjects experiencing persistent olfactory dysfunction: a 4-year follow-up study.","authors":"Tommaso Saccardo, Giuseppe Roccuzzo, Alessandro Fontana, Sonny Zampollo, Bruno Scarpa, Piero Nicolai, Alfonso Luca Pendolino, Carla Mucignat, Rosario Marchese-Ragona, Giancarlo Ottaviano","doi":"10.3389/fncir.2025.1538821","DOIUrl":"10.3389/fncir.2025.1538821","url":null,"abstract":"<p><strong>Background: </strong>Since the onset of the COVID-19 pandemic, chemosensory dysfunction (CD), including olfactory and taste quantitative dysfunction (OD/TD), has emerged as a prevalent and early symptom in SARS-CoV-2-infected subjects. This study explores the prevalence, duration, and recovery trajectory of COVID-19-related olfactory dysfunction (C19OD), with a specific focus on the four-year follow-up.</p><p><strong>Methods: </strong>Using a combination of psychophysical tests (Sniffin' sticks) and patient-reported outcome measures (sVAS and tVAS), 83 participants were prospectively evaluated for OD and parosmia. Factors influencing long-term olfactory recovery were analysed.</p><p><strong>Results: </strong>Baseline assessments revealed OD in 56.6% of patients, with progressive improvement observed over 4 years. At the four-year follow-up, 92.3% of patients recovered their olfaction while the remaining still reported hyposmia. Younger age and olfactory training were found to be favourable prognostic factors.</p><p><strong>Conclusion: </strong>Our findings show that, despite most individuals with C19OD recover olfaction within the first year, a subset of them continue to experience prolonged CD, demonstrating a slow, constant and meaningful improvement over years. This prolonged recovery period highlights the complexity of SARS-CoV-2's impact on olfactory function and highlights the need of further research on CD pathophysiology with the aim to improve therapeutic approaches to C19OD.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1538821"},"PeriodicalIF":3.4,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119333","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":"Effects of blood flow restriction on motoneurons synchronization.","authors":"Mansour Taleshi, Franziska Bubeck, Leonardo Gizzi, Ivan Vujaklija","doi":"10.3389/fncir.2025.1561684","DOIUrl":"https://doi.org/10.3389/fncir.2025.1561684","url":null,"abstract":"<p><p>Blood flow restriction (BFR) is a peripheral intervention that induces transient and reversible physiological perturbations. While this intervention offers a unique model to explore neuromuscular responses in multiple contexts, its impact on neural input to motoneurons remains unclear. Here, the influence of BFR on muscle force control, behavior, and neural input to motoneurons during isometric-trapezoidal and isometric-sinusoidal little finger abduction precision tasks has been studied. Sixteen healthy participants performed the tasks under pre-BFR, during BFR, and at two post-BFR conditions. High-density surface electromyography (EMG) was recorded from the abductor digiti minimi muscle, and motor unit spike trains (MUST) were decomposed using blind source separation technique. Coherence between cumulative spike trains (CSTs) of identified motor units was calculated to assess common synaptic input in the delta and alpha frequency bands. As expected, during BFR application, participants reported higher level of discomfort and significant deterioration in force-tracking performance, as measured using root mean square error (RMSE). Following the BFR release, the level of discomfort, along with impaired neuromuscular performance were reduced to pre-BFR condition. Coherence analysis revealed a prominent peak in the alpha band. The mean z-score coherence in the alpha band showed a reduction of 27% for isometric-trapezoidal and 31% for isometric-sinusoidal conditions from pre-BFR to BFR, followed by a rebound post-BFR intervention with increases of 13% and 20%, respectively. In the delta band, coherence values were consistently higher during sinusoidal tasks compared to trapezoidal ones. These findings indicate that brief BFR application led to decrease in motoneuron synchronization and force control precision likely due to desensitization as shown by changes in coherence alpha band.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1561684"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077309","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":"Acetylcholine in the hippocampus: problems and achievements.","authors":"Yulia V Dobryakova, Alexey P Bolshakov, Tinna Korotkova, Andrey V Rozov","doi":"10.3389/fncir.2025.1491820","DOIUrl":"https://doi.org/10.3389/fncir.2025.1491820","url":null,"abstract":"<p><p>Cholinergic septohippocampal projections originating from the medial septal area (MSA) play a critical role in regulating attention, memory formation, stress responses, and synaptic plasticity. Cholinergic axons from the MSA extensively innervate all hippocampal regions, providing a structural basis for the simultaneous release of acetylcholine (ACh) across the entire hippocampus. However, this widespread release appears inconsistent with the specific functional roles that ACh is thought to serve during distinct behaviors. A key unresolved question is how the dynamics of ACh tissue concentrations determine its ability to activate different receptor types and coordinate individual synaptic pathways. Here, we highlight several debated issues, including the potential intrinsic source of ACh within the hippocampus - such as cholinergic interneurons - and the co-release of ACh with GABA. Furthermore, we discuss recent findings on <i>in vivo</i> ACh concentration dynamics, which present a new dilemma for understanding ACh signaling in the hippocampus: the contrast between \"global\" ACh release, driven by synchronous activation of MSA neurons, and \"local\" release, which may be influenced by yet unidentified factors.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1491820"},"PeriodicalIF":3.4,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077308","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 innexin 7 gap junction protein contributes to synchronized activity in the <i>Drosophila</i> antennal lobe and regulates olfactory function.","authors":"Nicolás Fuenzalida-Uribe, Sergio Hidalgo, Bryon Silva, Saurin Gandhi, David Vo, Parham Zamani, Todd C Holmes, Sercan Sayin, Ilona C Grunwald Kadow, Dafni Hadjieconomou, Diane K O'Dowd, Jorge M Campusano","doi":"10.3389/fncir.2025.1563401","DOIUrl":"https://doi.org/10.3389/fncir.2025.1563401","url":null,"abstract":"<p><p>In the mammalian olfactory bulb (OB), gap junctions coordinate synchronous activity among mitral and tufted cells to process olfactory information. In insects, gap junctions are also present in the antennal lobe (AL), a structure homologous to the mammalian OB. The invertebrate gap junction protein ShakB contributes to electrical synapses between AL projection neurons (PNs) in <i>Drosophila</i>. Other gap junction proteins, including innexin 7 (Inx7), are also expressed in the <i>Drosophila</i> AL, but little is known about their contribution to intercellular communication during olfactory information processing. In this study, we report spontaneous calcium transients in PNs grown in cell culture that are highly synchronous when these neurons are physically connected. RNAi-mediated knockdown of Inx7 in cultured PNs blocks calcium transient neuronal synchronization. <i>In vivo</i>, downregulation of Inx7 in the AL impairs both vinegar-induced electrophysiological calcium responses and behavioral responses to this appetitive stimulus. These results demonstrate that Inx7-encoded gap junctions functionally coordinate PN activity and modulate olfactory information processing in the adult <i>Drosophila</i> AL.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1563401"},"PeriodicalIF":3.4,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002423","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":"Brain-wide connections of the parvicellular subdivision of the basolateral and basomedial amygdaloid nuclei in the rats.","authors":"Ge Zhu, Sheng-Qiang Chen, Run-Zhe Ma, Hui-Ru Cai, Jin-Yuan Zhang, Yi-Min Peng, Dian Lian, Song-Lin Ding","doi":"10.3389/fncir.2025.1575232","DOIUrl":"https://doi.org/10.3389/fncir.2025.1575232","url":null,"abstract":"<p><p>As the core area of emotion regulation, the amygdala is involved in and regulates many related behaviors, such as fear, anxiety, depression, as well as reward, learning, and memory. Most previous connectional studies have focused on the anterior and middle parts of the basolateral nucleus (BL) and basomedial nucleus (BM) of the amygdala. Little is known about the brain-wide connections of the posterior part of the BL and BM (termed parvicellular subdivision of the BL and BM, i.e., BLpc and BMpc). In this study, brain-wide afferent and efferent projections of the BLpc and BMpc in the rats are investigated using both retrograde and anterograde tracing methods. Both common and differential connections of the BLpc and BMpc are revealed. Major common inputs of both regions originate from the ventral hippocampal CA1 and prosubiculum, sublenticular extended amygdala, anterior basomedial nucleus, midline thalamic nuclei, endopiriform nucleus, dorsal raphe, piriform cortex and lateral entorhinal cortex. The BLpc receives preferential inputs from agranular insular cortex, amygdalopiriform transition area, periaqueductal gray, parataenial nucleus and anterior cortical nucleus of the amygdala. The BMpc preferentially receives its inputs from the peripeduncular nucleus, paraventricular nucleus of thalamus, ventromedial hypothalamic nucleus (VMH), caudal bed nucleus of stria terminalis (BST), medial amygdaloid nucleus and posterior cortical nucleus of the amygdala. Major differential outputs of the BLpc and BMpc are also obvious. The BLpc projects mainly to nucleus accumbens, rostral BST, lateral central amygdaloid nucleus (Ce), intermediate BL and BM. The BMpc sends its main outputs to VMH, medial Ce, caudal BST, prosubiculum, and perirhinal-ectorhinal cortices. These major findings are further confirmed with anterograde viral tracing in mice. Compared with previous findings in monkeys, our findings in rodents suggest that the BLpc and BMpc have overall similar connectional patterns across species. In addition, some gene markers for BM subdivisions are identified. All these findings would provide an important anatomical basis for the understanding of emotion-related neuronal circuits and diseases and for cross-species comparison of the subcircuits in amygdaloid complex.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1575232"},"PeriodicalIF":3.4,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974114","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":"Editorial: Circuits plasticity in neurodegenerative disorders: targeting mood disorders.","authors":"Yvan M Vachez, Philippe Huot, Robin Magnard","doi":"10.3389/fncir.2025.1592657","DOIUrl":"https://doi.org/10.3389/fncir.2025.1592657","url":null,"abstract":"","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1592657"},"PeriodicalIF":3.4,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12037615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968372","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 as a predictive coding modulator that enhances feedforward over feedback transmission.","authors":"Shinichi Kumagai, Tomoyo Isoguchi Shiramatsu, Kensuke Kawai, Hirokazu Takahashi","doi":"10.3389/fncir.2025.1568655","DOIUrl":"https://doi.org/10.3389/fncir.2025.1568655","url":null,"abstract":"<p><p>Vagus nerve stimulation (VNS) has emerged as a promising therapeutic intervention across various neurological and psychiatric conditions, including epilepsy, depression, and stroke rehabilitation; however, its mechanisms of action on neural circuits remain incompletely understood. Here, we present a novel theoretical framework based on predictive coding that conceptualizes VNS effects through differential modulation of feedforward and feedback neural circuits. Based on recent evidence, we propose that VNS shifts the balance between feedforward and feedback processing through multiple neuromodulatory systems, resulting in enhanced feedforward signal transmission. This framework integrates anatomical pathways, receptor distributions, and physiological responses to explain the influence of the VNS on neural dynamics across different spatial and temporal scales. Vagus nerve stimulation may facilitate neural plasticity and adaptive behavior through acetylcholine and noradrenaline (norepinephrine), which differentially modulate feedforward and feedback signaling. This mechanistic understanding serves as a basis for interpreting the cognitive and therapeutic outcomes across different clinical conditions. Our perspective provides a unified theoretical framework for understanding circuit-specific VNS effects and suggests new directions for investigating their therapeutic mechanisms.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1568655"},"PeriodicalIF":3.4,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998469","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 cerebellar deep nuclei: a patch for rate codes?","authors":"Mike Gilbert, Anders Rasmussen","doi":"10.3389/fncir.2025.1548123","DOIUrl":"https://doi.org/10.3389/fncir.2025.1548123","url":null,"abstract":"<p><p>Neural firing rates are thought to represent values which code information. There are drawbacks with using biophysical events to represent numbers. (1) Rate code (like any sequence) is inherently slow to read. (2) At short intervals, the code becomes unintelligible biophysical noise. (3) Transmission times. The vital contribution of the cerebellum to skilled execution and coordination of movements requires precision timing. We present a theory supported by modeling that the output cell group of the cerebellar network is a practical solution to timing problems. In this role, it converts irregularly-patterned firing of Purkinje cells into an effectively instantaneous rate received by output cells, transforms the rate into linear analog modulation of output cell firing, synchronizes firing between output cells, and compensates for lag caused by extracerebellar transmission times. The cerebellum is widely connected to the midbrain and the cerebral cortex and involved in cognitive functions. Modular network wiring suggests that the cerebellum may perform the same computation on input from all sources regardless of where it is from. If so, and the deep cerebellar nuclei make the same contribution to the role of the cerebellum in other functions, an understanding of motor function would also provide insight into the substrate of cognitive functions.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1548123"},"PeriodicalIF":3.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994275","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":"Anatomical mapping of whole-brain monosynaptic inputs to the orbitofrontal cortex.","authors":"Mei Yang, Hailing Yang, Lang Shen, Tonghui Xu","doi":"10.3389/fncir.2025.1567036","DOIUrl":"https://doi.org/10.3389/fncir.2025.1567036","url":null,"abstract":"<p><p>The orbitofrontal cortex (ORB) exhibits a complex structure and diverse functional roles, including emotion regulation, decision-making, and reward processing. Structurally, it comprises three distinct regions: the medial part (ORBm), the ventrolateral part (ORBvl), and the lateral part (ORBl), each with unique functional attributes, such as ORBm's involvement in reward processing, ORBvl's regulation of depression-like behavior, and ORBl's response to aversive stimuli. Dysregulation of the ORB has been implicated in various psychiatric disorders. However, the neurocircuitry underlying the functions and dysfunctions of the ORB remains poorly understood. This study employed recombinant adeno-associated viruses (rAAV) and rabies viruses with glycoprotein deletion (RV-ΔG) to retrogradely trace monosynaptic inputs to three ORB subregions in male C57BL/6J mice. Inputs were quantified across the whole brain using fluorescence imaging and statistical analysis. Results revealed distinct input patterns for each ORB subregion, with significant contributions from the isocortex and thalamus. The ORBm received prominent inputs from the prelimbic area, agranular insular area, and hippocampal field CA1, while the ORBvl received substantial intra-ORB inputs. The ORBl exhibited strong inputs from the somatomotor and somatosensory areas. Thalamic inputs, particularly from the mediodorsal nucleus and submedial nucleus of the thalamus, were widespread across all ORB subregions. These findings provide novel insights into the functional connectivity of ORB subregions and their roles in neural circuit mechanisms underlying behavior and psychiatric disorders.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1567036"},"PeriodicalIF":3.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004660","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}