{"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}
Natalie Lipari, Ashley Galfano, Shruti Venkatesh, Han Grezenko, Ivette M Sandoval, Fredric P Manfredsson, Christopher Bishop
{"title":"Corrigendum: The effects of chemogenetic targeting of serotonin-projecting pathways on L-DOPA-induced dyskinesia and psychosis in a bilateral rat model of Parkinson's disease.","authors":"Natalie Lipari, Ashley Galfano, Shruti Venkatesh, Han Grezenko, Ivette M Sandoval, Fredric P Manfredsson, Christopher Bishop","doi":"10.3389/fncir.2025.1593235","DOIUrl":"https://doi.org/10.3389/fncir.2025.1593235","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fncir.2024.1463941.].</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1593235"},"PeriodicalIF":3.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11996784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005119","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":"Development of the rodent prefrontal cortex: circuit formation, plasticity, and impacts of early life stress.","authors":"Xinyi Chen, Yuri Kim, Daichi Kawaguchi","doi":"10.3389/fncir.2025.1568610","DOIUrl":"https://doi.org/10.3389/fncir.2025.1568610","url":null,"abstract":"<p><p>The prefrontal cortex (PFC), located at the anterior region of the cerebral cortex, is a multimodal association cortex essential for higher-order brain functions, including decision-making, attentional control, memory processing, and regulation of social behavior. Structural, circuit-level, and functional abnormalities in the PFC are often associated with neurodevelopmental disorders. Here, we review recent findings on the postnatal development of the PFC, with a particular emphasis on rodent studies, to elucidate how its structural and circuit properties are established during critical developmental windows and how these processes influence adult behaviors. Recent evidence also highlights the lasting effects of early life stress on the PFC structure, connectivity, and function. We explore potential mechanisms underlying these stress-induced alterations, with a focus on epigenetic regulation and its implications for PFC maturation and neurodevelopmental disorders. By integrating these insights, this review provides an overview of the developmental processes shaping the PFC and their implications for brain health and disease.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1568610"},"PeriodicalIF":3.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11979153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005753","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 diversity and plasticity of descending motor pathways rewired after stroke and trauma in rodents.","authors":"Takahiro Inoue, Masaki Ueno","doi":"10.3389/fncir.2025.1566562","DOIUrl":"10.3389/fncir.2025.1566562","url":null,"abstract":"<p><p>Descending neural pathways to the spinal cord plays vital roles in motor control. They are often damaged by brain injuries such as stroke and trauma, which lead to severe motor impairments. Due to the limited capacity for regeneration of neural circuits in the adult central nervous system, currently no essential treatments are available for complete recovery. Notably, accumulating evidence shows that residual circuits of the descending pathways are dynamically reorganized after injury and contribute to motor recovery. Furthermore, recent technological advances in cell-type classification and manipulation have highlighted the structural and functional diversity of these pathways. Here, we focus on three major descending pathways, namely, the corticospinal tract from the cerebral cortex, the rubrospinal tract from the red nucleus, and the reticulospinal tract from the reticular formation, and summarize the current knowledge of their structures and functions, especially in rodent models (mice and rats). We then review and discuss the process and patterns of reorganization induced in these pathways following injury, which compensate for lost connections for recovery. Understanding the basic structural and functional properties of each descending pathway and the principles of the induction and outcome of the rewired circuits will provide therapeutic insights to enhance interactive rewiring of the multiple descending pathways for motor recovery.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1566562"},"PeriodicalIF":3.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795193","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":"Reduced GABAergic inhibition and impaired synapse elimination by neuroligin-2 deletion from Purkinje cells of the developing cerebellum.","authors":"Esther Suk King Lai, Naofumi Uesaka, Taisuke Miyazaki, Kouichi Hashimoto, Masahiko Watanabe, Masanobu Kano","doi":"10.3389/fncir.2025.1530141","DOIUrl":"10.3389/fncir.2025.1530141","url":null,"abstract":"<p><p>Functionally mature neural circuits are shaped during postnatal development by eliminating redundant synapses formed around birth. This process is known as synapse elimination and requires a proper balance of excitation and inhibition. Neuroligin-2 (NL2) is a postsynaptic cell adhesion molecule required for the formation, maintenance, and function of inhibitory synapses. However, how NL2 regulates synapse elimination during postnatal development is largely unknown. Here we report that the deletion of NL2 from Purkinje cells (PCs) in the cerebellum impairs the developmental elimination of redundant climbing fiber (CF) to PC synapses. In global NL2-knockout (KO) mice, GABAergic inhibition to PCs was attenuated and CF synapse elimination was impaired after postnatal day 10 (P10). These phenotypes were restored by the expression of NL2 into PCs of NL2-KO mice. Moreover, microRNA-mediated knockdown of NL2 specifically from PCs during development caused attenuated inhibition and impaired CF synapse elimination. In PCs innervated by \"strong\" and \"weak\" CFs, calcium transients elicited by \"weak\" CFs were enhanced in NL2-deficient PCs, suggesting that excess calcium signaling permits the survival of redundant \"weak\" CF synapses. We conclude that NL2 is crucial for maintaining inhibitory synaptic function and properly eliminating redundant CF synapses during postnatal development.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1530141"},"PeriodicalIF":3.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752067","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":"Surrogate data analyses of the energy landscape analysis of resting-state brain activity.","authors":"Yuki Hosaka, Takemi Hieda, Ruixiang Li, Kenji Hayashi, Koji Jimura, Teppei Matsui","doi":"10.3389/fncir.2025.1500227","DOIUrl":"10.3389/fncir.2025.1500227","url":null,"abstract":"<p><p>The spatiotemporal dynamics of resting-state brain activity can be characterized by switching between multiple brain states, and numerous techniques have been developed to extract such dynamic features from resting-state functional magnetic resonance imaging (fMRI) data. However, many of these techniques are based on momentary temporal correlation and co-activation patterns and merely reflect linear features of the data, suggesting that the dynamic features, such as state-switching, extracted by these techniques may be misinterpreted. To examine whether such misinterpretations occur when using techniques that are not based on momentary temporal correlation or co-activation patterns, we addressed Energy Landscape Analysis (ELA) based on pairwise-maximum entropy model (PMEM), a statistical physics-inspired method that was designed to extract multiple brain states and dynamics of resting-state fMRI data. We found that the shape of the energy landscape and the first-order transition probability derived from ELA were similar between real data and surrogate data suggesting that these features were largely accounted for by stationary and linear properties of the real data without requiring state-switching among locally stable states. To confirm that surrogate data were distinct from the real data, we replicated a previous finding that some topological properties of resting-state fMRI data differed between the real and surrogate data. Overall, we found that linear models largely reproduced the first order ELA-derived features (i.e., energy landscape and transition probability) with some notable differences.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1500227"},"PeriodicalIF":3.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752081","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":"Sparse connectivity enables efficient information processing in cortex-like artificial neural networks.","authors":"Rieke Fruengel, Marcel Oberlaender","doi":"10.3389/fncir.2025.1528309","DOIUrl":"10.3389/fncir.2025.1528309","url":null,"abstract":"<p><p>Neurons in cortical networks are very sparsely connected; even neurons whose axons and dendrites overlap are highly unlikely to form a synaptic connection. What is the relevance of such sparse connectivity for a network's function? Surprisingly, it has been shown that sparse connectivity impairs information processing in artificial neural networks (ANNs). Does this imply that sparse connectivity also impairs information processing in biological neural networks? Although ANNs were originally inspired by the brain, conventional ANNs differ substantially in their structural network architecture from cortical networks. To disentangle the relevance of these structural properties for information processing in networks, we systematically constructed ANNs constrained by interpretable features of cortical networks. We find that in large and recurrently connected networks, as are found in the cortex, sparse connectivity facilitates time- and data-efficient information processing. We explore the origins of these surprising findings and show that conventional dense ANNs distribute information across only a very small fraction of nodes, whereas sparse ANNs distribute information across more nodes. We show that sparsity is most critical in networks with fixed excitatory and inhibitory nodes, mirroring neuronal cell types in cortex. This constraint causes a large learning delay in densely connected networks which is eliminated by sparse connectivity. Taken together, our findings show that sparse connectivity enables efficient information processing given key constraints from cortical networks, setting the stage for further investigation into higher-order features of cortical connectivity.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"19 ","pages":"1528309"},"PeriodicalIF":3.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779614","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}