Frontiers In Neuroanatomy[JOURNAL]
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200 papers
Editorial: Updates and discussions about basal ganglia and their circuits.
Cavalcanti JRLP, do Nascimento-Júnior ES, Huang ZL … +1 more , Bhagwandin A
Front Neuroanat · 2026 · PMID 42394641 · Full text
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TC2-Res: a structured fusion of tract-level and connectome-level brain imaging in small-sample cohorts of athletes.
Shi Y, Chen L, Huang M … +3 more , Huang Z, Ou J, Zeng J
Front Neuroanat · 2026 · PMID 42317642 · Full text
Combining diffusion tract descriptors with structural connectome descriptors may help characterize athlete-related brain imaging patterns; however, this approach is challenging in small-sample studies, where flexible lea...
Combining diffusion tract descriptors with structural connectome descriptors may help characterize athlete-related brain imaging patterns; however, this approach is challenging in small-sample studies, where flexible learned models can easily overfit. In such settings, simple linear classifiers often serve as strong baselines, although they do not explicitly encode the anatomical correspondence between tract-level microstructural descriptors and connectome-level organization. To address this gap, we introduce Tensor Connectome Consistency Residual (TC2-Res), a lightweight structured fusion framework that combines pair-aware tract representations, global modality branches, family-level encoders, and a tract-connectome consistency regularizer that encourages matched anatomical families to align in a shared latent space. In a small cohort of collegiate athletes, TC2-Res achieved a slightly higher mean balanced accuracy compared to a matched naive learned fusion baseline on the primary football-vs.-others task, whereas a classical linear support vector machine (SVM) remained the strongest overall classifier. The observed performance gain was modest and inconsistent across folds, and evidence of improvement specifically attributable to the consistency term was limited. These results suggest that anatomically structured fusion represents a plausible lightweight design direction for learned multimodal classification in limited-data settings while also highlighting the continued strength of classical linear baselines in this regime.
Revisiting the clastosome: a stress-induced nuclear proteolytic compartment of mammalian cells.
Lafarga M, Berciano MT, Rueda N … +2 more , Cardona-Cortés S, Tapia O
Front Neuroanat · 2026 · PMID 42311938 · Full text
The nuclear ubiquitin proteasome system (UPS) is fundamental to maintaining proteostasis and ensuring the quality control of nuclear proteins. Within the nucleus, proteasomes are distributed throughout the nucleoplasm an...
The nuclear ubiquitin proteasome system (UPS) is fundamental to maintaining proteostasis and ensuring the quality control of nuclear proteins. Within the nucleus, proteasomes are distributed throughout the nucleoplasm and can aggregate into nuclear bodies. In 2002, our group provided the first description in mammalian cells of a specific subtype of nuclear body highly enriched in: (i) ubiquitin conjugates, (ii) the proteolytically active 20S and 19S regulatory complexes of the 26S proteasome, (iii) the molecular chaperone Hsp70, and (iv) proteasome substrates. We coined the term clastosome to define this nuclear proteolytic center of the UPS. Clastosomes exhibit dynamic behavior, and their formation is transiently and robustly induced in mammalian neurons during osmotic stress, coinciding with enhanced proteasomal activity. Subsequent studies have confirmed and mechanistically expanded our understanding of these nuclear proteolytic centers, which are now recognized as nuclear condensates formed via liquid-liquid phase separation mechanisms. Notably, PML nuclear bodies can establish interactions with clastosomes, thereby linking the PML protein and the SUMOylation pathway with UPS-mediated protein degradation. The association between PML nuclear bodies and clastosomes has been implicated in the clearance of toxic mutant proteins associated with certain neurodegenerative diseases. This review examines the structure, composition, and dynamic regulation of clastosomes, focusing on their modulation during stress responses and neurodegeneration. Given the essential role of nuclear proteolytic centers in proteostasis regulation, a better understanding of mechanisms that modulate their assembly may offer therapeutic strategies for neurodegenerative proteinopathies and other pathologies.
Intrinsic elaboration of prefrontal modularity: a dual-control model of axon bundling and synaptic docking.
Yamamori T, Watakabe A, Skibbe H
Front Neuroanat · 2026 · PMID 42311937 · Full text
The evolutionary expansion of the primate prefrontal cortex (PFC) presents a profound biological enigma: how does this region achieve a highly ordered, modular architecture in the absence of direct dense sensory template...
The evolutionary expansion of the primate prefrontal cortex (PFC) presents a profound biological enigma: how does this region achieve a highly ordered, modular architecture in the absence of direct dense sensory templates that govern primary sensory areas? In this review, we synthesize classical neuroanatomical frameworks with recent advances in spatial transcriptomics and connectomics to delineate a model of intrinsic elaboration. We propose that PFC modularity emerges from a developmental program facilitated by expansion of the outer subventricular zone (OSVZ) and the legacy of whole-genome duplication (2R-WGD). Central to this proposal is a "Dual-Control Model" of circuit assembly, inferred by integrating anatomical tracer data with spatial and spatiotemporal transcriptomic datasets. This framework suggests that long-range connectivity is established through pre-target axon bundling (fasciculation), governed by a high-dimensional navigation code (e.g., ephrin/Eph, PCDH11X, PCDH17, ROBO2), while these bundles are anchored onto vertical columnar scaffolds through synaptic docking mechanisms (e.g., CBLN2, cadherins). By contrasting the PFC with the map-driven visual system, point-driven olfactory system, and layer-driven hippocampus, we argue that PFC uniqueness lies not in novel genes but in a combinatorial logic of a shared molecular toolkit, which can be understood as intrinsic elaboration. This framework may facilitate the emergence of a cognitive scaffold under relatively weak external sensory constraints. These molecular systems are considered to operate in concert with activity-dependent developmental refinement rather than independently of neural activity.
Selective enrichment of TCF4 in GABAergic neurons during postnatal primate development.
Burette AC, Hipp RI, Salvador S … +7 more , Gonzalez Ramirez C, Patel RKR, Salvador NR, Dasher KA, Bennett J, Amaral DG, Philpot BD
Front Neuroanat · 2026 · PMID 42238855 · Full text
The transcription factor 4 () gene is essential for brain development, and its disruption causes Pitt-Hopkins syndrome. Common genetic variants in also confer risk for schizophrenia and related psychiatric disorders. Wh...
The transcription factor 4 () gene is essential for brain development, and its disruption causes Pitt-Hopkins syndrome. Common genetic variants in also confer risk for schizophrenia and related psychiatric disorders. While the developmental roles of TCF4 are well established, its postnatal functions remain poorly defined, particularly during the prolonged maturation of the primate neocortex, when many neuropsychiatric symptoms first emerge. Here, we mapped cell-type-specific TCF4 expression across postnatal development in rhesus macaque neocortex using immunofluorescence, and hybridization. We also re-analyzed public bulk-tissue and single-nucleus transcriptomic datasets spanning 16 brain regions in both humans and macaques. TCF4 was predominantly neuronal, with minimal expression in microglia, oligodendrocytes, and astrocytes. In late gestation, TCF4 was broadly expressed in excitatory and inhibitory neurons, but expression declined with maturation and became selectively enriched in inhibitory populations. By young adulthood, nuclear TCF4 levels were highest in somatostatin-positive and vasoactive intestinal peptide-positive interneurons, intermediate in parvalbumin interneurons (~6-fold above non-GABAergic cells), and lowest in cholecystokinin interneurons (~4-fold above non-GABAergic cells). This interneuron-subtype hierarchy was independently reproduced by single-nucleus RNA sequencing across all neocortical regions. Together, these findings position mature GABAergic interneurons as the principal site of TCF4 function in the primate neocortex, providing a cellular framework for linking TCF4 dysfunction to cortical circuit imbalance in Pitt-Hopkins syndrome and psychiatric disease.
ATF3-based peripheral neural tract tracing.
Gautron L
Front Neuroanat · 2026 · PMID 42221577 · Full text
Defining neural connectivity between peripheral organs and the nervous system remains a fundamental challenge. While neural tract tracing techniques are well established and highly effective in the central nervous system...
Defining neural connectivity between peripheral organs and the nervous system remains a fundamental challenge. While neural tract tracing techniques are well established and highly effective in the central nervous system, their application in peripheral tissues-particularly through retrograde approaches-continues to generate controversy. This article highlights an alternative approach based on the neuronal injury response. Specifically, I discuss the use of activating transcription factor 3 (ATF3), a molecular marker robustly upregulated in neurons following axonal injury, as an indirect means of identifying organ-specific innervation. By integrating classical and injury-induced approaches, this framework may help resolve longstanding debates regarding visceral innervation and improve the reliability of circuit-mapping strategies in the peripheral nervous system.
Stereological evaluation of the neuroprotective effects of curcumin on the spinal cord in a streptozotocin-induced diabetic rat model.
Delibaş B, Keleş Aİ, Kaplan AA … +5 more , Kocaman B, Altun G, Tüfekci KK, Aktaş A, Kaplan S
Front Neuroanat · 2026 · PMID 42148160 · Full text
INTRODUCTION: This study examined how curcumin influences spinal cord morphological parameters in rats with STZ-induced diabetes using unbiased stereological methods. METHODS: Fifty-six female Wistar albino rats were ran...
INTRODUCTION: This study examined how curcumin influences spinal cord morphological parameters in rats with STZ-induced diabetes using unbiased stereological methods. METHODS: Fifty-six female Wistar albino rats were randomly divided into seven experimental groups ( = 8): Control, Sham, Curcumin, Diabetes Mellitus (DM), DM + Curcumin after 7 days (DC1), DM + Curcumin after 21 days (DC2), and DM + Curcumin simultaneously (DC3). Diabetes was induced via a single intraperitoneal dose of STZ (50 mg/kg). Curcumin was administered at a dose of 30 mg/kg via intragastric gavage for 14 consecutive days. C3-C5 spinal segments were collected at the end of the experiment, processed for histology, and stained with toluidine blue and cresyl violet for stereological analysis. Neuronal quantification in the anterior horn was performed using physical fractionator. The volume fractions of the spinal cord, including white matter (WM/total volume) and gray matter (GM/total volume), were estimated using the Cavalieri's principle. RESULTS: The diabetic (DM) group showed a significant reduction in motor neuron number compared with the Control group ( = 0.019), demonstrating diabetes-induced neuronal loss. In contrast, the DC2 treatment group showed a significant increase in motor neuron counts compared with DM ( = 0.04), suggesting a possible neuroprotective effect of curcumin. Total spinal cord volume did not differ significantly among groups. WM/Total ratio decreased in the Sham group but increased with curcumin (DC3). GM/Total ratio was lower in DC3 than Sham, and curcumin produced a non-significant improvement compared with diabetic rats. Increased caspase-3 immunoreactivity in the diabetic group indicates activation of apoptotic pathways, consistent with the observed reduction in motor neuron number and soma size. Furthermore, the marked increase in GFAP immunoreactivity, particularly in the DC2 group, reflects astrocyte activation and a reactive gliosis, which are commonly associated with metabolic stress and neuroinflammation in diabetic conditions. DISCUSSION: Curcumin administration partially mitigated spinal motor neuron loss induced by experimental diabetes. The timing of curcumin treatment influenced its efficacy. These findings suggest that curcumin may have therapeutic potential for preventing diabetes-induced spinal cord neurodegeneration.
Perisomatic innervation on the semilunar granule cells and outer molecular layer granule cells of the dentate gyrus of the mouse.
Rovira-Esteban L, Vieco-Martí I, Herraiz-Cabanes J … +4 more , Varea E, Nacher J, Crespo C, Blasco-Ibáñez JM
Front Neuroanat · 2026 · PMID 42136574 · Full text
Semilunar granule cells in the dentate gyrus represent a distinct type of granule cell, distinguished by their unique morphology and physiology. These cells are located within the inner molecular layer and the upper juxt...
Semilunar granule cells in the dentate gyrus represent a distinct type of granule cell, distinguished by their unique morphology and physiology. These cells are located within the inner molecular layer and the upper juxta-granule cell layer of the dentate gyrus. The presence of a smaller number of granule cells has also been observed in the outer molecular layer; however, the information regarding these cells is limited. In the present study, the perisomatic innervation that these two types of granule cells receive was characterized using confocal and electron microscopy. Our findings revealed that both semilunar granule cells and outer molecular layer granule cells receive substantial excitatory and inhibitory perisomatic contacts. The inhibitory contacts are derived from parvalbumin fast-spiking cells and cholecystokinin regular-spiking cells. The origin of excitatory contacts has been traced to hilar mossy cells and supramammillary afferents.
Pulvinar subdivisions and connectivity patterns across primate species: a comparative perspective.
Soares JGM, Correia ARA, Gattass R … +1 more , Lima B
Front Neuroanat · 2026 · PMID 42130669 · Full text
With the advances in our ability to perturb brain activity in recent years, new stimulation techniques have become essential tools in human neuroscience. Non-invasive stimulation methods, such as transcranial magnetic st...
With the advances in our ability to perturb brain activity in recent years, new stimulation techniques have become essential tools in human neuroscience. Non-invasive stimulation methods, such as transcranial magnetic stimulation (TMS), as well as deep brain stimulation (DBS) delivered invasively to access deep brain structures, have been applied in both basic and clinical research and in the treatment of neurological conditions including Parkinson's disease, essential tremor and epilepsy. In the context of epilepsy, neuromodulatory interventions have demonstrated encouraging results in reducing seizure frequency, bringing attention to the thalamic pulvinar nucleus as a potential target for stimulation in drug-resistant cases. To advance these and future therapies, it is necessary to have a more detailed understanding of the subdivisions and connectivity patterns of these nuclei. Although some human studies have employed diffusion imaging and fMRI, much of the current knowledge of pulvinar connectivity still comes from non-human primate (NHP) studies. The aim of this study is to review the cortico-pulvinar connectivity patterns of distinct pulvinar subregions across NHP species, alongside available human studies, to help optimize future basic and clinical research.
Layer-specific cellular composition of mouse primary somatosensory and human temporal cortex: a direct 3D confocal counting approach.
Plaza-Alonso S, Alonso-Nanclares L, Tapia-González S … +3 more , Fernández-García L, Kastanauskaite A, DeFelipe J
Front Neuroanat · 2026 · PMID 42109839 · Full text
Accurate quantification of cellular composition is fundamental to understanding the structural and functional organization of the cerebral cortex. In the present study, we quantified the proportions of neurons, glia, and...
Accurate quantification of cellular composition is fundamental to understanding the structural and functional organization of the cerebral cortex. In the present study, we quantified the proportions of neurons, glia, and vascular cells (primarily endothelial cells) across the full cortical thickness (layers I-VI) of the mouse primary somatosensory cortex (S1HL) and the human temporal cortex (BA21) using immunocytochemical techniques and a direct 3D counting method. Over 25,000 cells in the mouse and 13,000 cells in the human cortex were individually identified and classified. For this purpose, we utilized EspINA software, which enables precise cell identification and volumetric analysis while preserving laminar and spatial context. Our results reveal marked species-specific differences in cellular proportions: neurons represent approximately 60% of all cells in the mouse S1HL but only 30% in the human BA21. These differences are reflected in the glia-to-neuron ratio (GNR) and non-neuron-to-neuron ratio (nNNR), which were consistently below 1.0 in the mouse (GNR: 0.4; nNNR: 0.6) but significantly higher in the human samples (GNR: 1.5; nNNR: 2.3). By overcoming the limitations of traditional stereological and tissue-homogenization techniques, this study provides a detailed laminar characterization of the cellular composition in these particular cortical regions (mouse S1HL and human BA21).
A narrative review of motor control dual pathways: the corticospinal and reticulospinal tracts in synergy and differentiation.
Xing Y, Liu J, Wu L … +2 more , Zhang K, Yang S
Front Neuroanat · 2026 · PMID 42039090 · Full text
The corticospinal tract (CST) and reticulospinal tract (RST) represent the core descending pathways within the central nervous system for motor control. This review elucidates the anatomical and functional interplay. Ana...
The corticospinal tract (CST) and reticulospinal tract (RST) represent the core descending pathways within the central nervous system for motor control. This review elucidates the anatomical and functional interplay. Anatomically, the CST and RST fibers are spatially proximate within the spinal cord and are integrated into a continuous regulatory axis via the corticoreticular pathway. Functionally, they exhibit both synergy and specialization: the CST primarily governs contralateral distal limb fine motor control, whereas the RST, operating in a bilateral mode, regulates axial and proximal body movements, postural stability, and adaptation to strength training. Notably, following CST damage (e.g., stroke or spinal cord injury), the RST demonstrates remarkable plasticity and serves as a critical substrate for functional compensation and recovery. Furthermore, an imbalance in CST-RST function has been implicated in the pathophysiology of conditions such as post-stroke spasticity and multiple sclerosis. Therapeutic strategies targeting the CST-RST network, including neuromodulation and molecular interventions aimed at promoting axonal regeneration and modulating network excitability, present promising new directions for the treatment of neurological disorders. Future research should focus on deciphering the specific interactions at the spinal interneuron level to advance the development of precise rehabilitation strategies.
Maternal gut dysbiosis is associated with altered enteric and cortical inhibitory circuit development.
Nakhal MM, Nafees F, Mydeen AB … +9 more , Al Ali A, Baloch S, Alkhalaf R, Albalas HM, Albalas GM, Alharbi G, Statsenko Y, Marzouka NA, Hamad MIK
Front Neuroanat · 2026 · PMID 42039089 · Full text
INTRODUCTION: Maternal environmental factors critically influence neural circuit maturation during early development. The maternal gut microbiota has emerged as an important upstream regulator of offspring neurodevelopme...
INTRODUCTION: Maternal environmental factors critically influence neural circuit maturation during early development. The maternal gut microbiota has emerged as an important upstream regulator of offspring neurodevelopment, yet its role in shaping the structural organization of enteric and cortical inhibitory circuits remains poorly defined. Here, we examined whether gestational disruption of the maternal gut microbiota is associated with alterations in parallel enteric and cortical inhibitory circuit development. METHODS: Maternal gut dysbiosis was induced in pregnant GAD67-GFP mice by oral vancomycin administration during gestation. Maternal and offspring microbiota were analyzed using full-length 16S rRNA gene sequencing to assess microbial diversity and vertical transmission. Offspring were examined at postnatal day 14 for intestinal morphology, altered barrier integrity, and enteric nervous system (ENS) organization. Cortical inhibitory circuits were analyzed by quantifying GAD67-positive interneuron density and performing three-dimensional morphological reconstruction in layers II/III of the somatosensory cortex, motor cortex, medial entorhinal cortex, and CA1 region of the hippocampus. RESULTS: Maternal dysbiosis significantly reduced microbial diversity and disrupted maternal-offspring microbial transmission. These changes were associated with impaired intestinal development, including reduced crypt height, thinning of the muscularis propria, fragmented Claudin-1 expression, and reduced Auerbach's plexus area without changes in neuronal density, indicating altered enteric network organization. In the brain, maternal dysbiosis induced region-specific cortical vulnerability, with reduced dendritic length and branching of GAD67-positive interneurons in the somatosensory and motor cortices, while interneuron morphology in the medial entorhinal cortex and hippocampus was preserved. Interneuron density was selectively reduced in the motor cortex. DISCUSSION: These findings indicate that gestational maternal dysbiosis is associated with co-occurring structural alterations in intestinal and cortical inhibitory systems, selectively affecting inhibitory circuit architecture in sensorimotor regions. While the present model does not isolate microbiota-specific mechanisms from potential antibiotic-induced maternal physiological changes, the data support an association between disrupted maternal microbial ecology and offspring enteric and cortical neuroanatomical development during early postnatal life. These findings should be interpreted as descriptive associations and do not establish mechanistic gut-brain interactions.
Folic acid modulates the Notch1/NF-κB pathway in a rat model of lipopolysaccharide-activated hippocampal microglia.
Abd El-Kader M, Farrag EAE, El-Gamal R … +7 more , El Nashar EM, Alshehri AM, Aldahhan RA, Al-Khater KM, El-Desouky S, El-Sherbeni MW, Ebrahim NA
Front Neuroanat · 2026 · PMID 42039088 · Full text
INTRODUCTION: Lipopolysaccharide (LPS) induces neuronal injury by stimulating microglia, which release pro-inflammatory markers and neurotoxic factors. Folate deficiency induces microglial activation and modulates nuclea...
INTRODUCTION: Lipopolysaccharide (LPS) induces neuronal injury by stimulating microglia, which release pro-inflammatory markers and neurotoxic factors. Folate deficiency induces microglial activation and modulates nuclear factor-κB (NF-κB) p65 and neurogenic locus Notch homolog protein 1 (Notch1) expression in the hippocampus. This study investigated the neuroprotective effect of folic acid against LPS-induced neurotoxicity in rats, focusing on its modulation of microglial activation and the Notch1, NF-κB, and p65 signaling pathways. METHODS: A total of 24 Sprague-Dawley male rats were assigned to four groups: control, folic acid, LPS, and folic acid + LPS. After sacrifice, the left cerebral hemisphere was subjected to histopathological assessment using hematoxylin and eosin (H&E) staining and immunohistochemical assessment using anti-GFAP, anti-Iba1, anti-cyclooxygenase-2 (COX-2), anti-tumor necrosis factor- (TNF-α), and anti-NF-κB antibodies. The hippocampus was extracted from the right hemisphere and used to assess the gene expression of Notch1, TNF-α, interleukin-6 (IL-6), and COX-2 markers using real-time reverse transcription PCR. RESULTS: Folic acid ameliorated LPS-induced neuronal damage in the hippocampus, suppressed microglial activation (GFAP and Iba-1), downregulated Notch1 and NF-κB p65, and improved neuroinflammatory responses (TNF-α, IL-6, and COX-2), regardless of the region. CONCLUSION: Folic acid exerted an equivalent neuroprotective effect in both the CA1 and CA3 regions by suppressing microglial activation and modulating the Notch1/NF-κB signaling pathway, thereby reducing neuroinflammation. These findings suggest that folic acid may serve as a potential adjuvant neuroprotective agent against inflammation-mediated neuronal injury.
The effect of complex double-axis rotation model on GABAergic neurons in caudal ventrolateral medulla of rats along the vestibulo-sympathetic reflex pathway.
Qi J, Chen C, Gao Q
Front Neuroanat · 2026 · PMID 42027889 · Full text
INTRODUCTION: Motion sickness is a common physiological disorder induced by with unusual movement exposure, characterized by conflicting motion signals that trigger vestibulo-sympathetic reflexes (VSR). These reflexes me...
INTRODUCTION: Motion sickness is a common physiological disorder induced by with unusual movement exposure, characterized by conflicting motion signals that trigger vestibulo-sympathetic reflexes (VSR). These reflexes mediate autonomic responses to motion-induced stress. Previous studies have implicated the vestibular nucleus complex and the caudal ventrolateral medulla (CVLM) in VSR modulation. GABA (γ-aminobutyric acid), the primary inhibitory neurotransmitter in the central nervous system (CNS), plays a key role in both cardiovascular regulation and vestibular function. However, the specific contribution of GABAergic structures to motion sickness-related cardiovascular responses remains unclear. METHODS: In this study, we combined retrograde tracing and immunofluorescence labeling to investigate GABAergic pathways using complex double-axis rotation model. Fluoro-Gold (FG) was injected into the CVLM, while biotinylated dextran amine (BDA) was delivered to the medial vestibular nuclei (MVe). RESULTS: Our results revealed a bilateral distribution of GABAergic neurons, predominantly within the caudal raphe nuclei. Notably, a subset of these neurons was activated (as indicated by Fos immunoreactivity) and projected to the CVLM (as shown by retrograde labeling with FG) under complex double-axis rotation model. Furthermore, these same neurons also received direct inputs from the MVe, as evidenced by their labeling with BDA. DISCUSSION: Our findings offer morphological evidence that GABAergic neurons in the caudal raphe nuclei participate in the cardiovascular responses evoked by motion sickness in a complex double-axis rotation model.
Neuroanatomical organization: the palato-pharyngeal complex as a sensory-motor hub.
Hong YS, Park YS
Front Neuroanat · 2026 · PMID 41982253 · Full text
The pharynx has traditionally been described as a musculo-membranous conduit involved in respiration and deglutition. From a neuroanatomical perspective, however, this region also represents a multi-nerve interface where...
The pharynx has traditionally been described as a musculo-membranous conduit involved in respiration and deglutition. From a neuroanatomical perspective, however, this region also represents a multi-nerve interface where somatic afferents of the trigeminal nerve (V) and visceral afferents of the glossopharyngeal (IX) and vagus (X) nerves converge. In this review, we use the term Palato-Pharyngeal Complex (PPC) to describe this anatomically integrated region and discuss its potential role as a sensory-motor interface associated with brainstem circuits involving the nucleus tractus solitarius (NTS) and nucleus ambiguus (NA). We highlight the coordinated activity of the tensor veli palatini (innervated by V3) and the levator veli palatini (innervated by X) as an example of somatic-visceral motor integration within this region. Building on existing models of brainstem central pattern generators, we discuss a hierarchical control framework in which brainstem circuits may be modulated by supranuclear influences from cortical and limbic systems. Within this context, we introduce the concept of a Reflex-Volition Coupling (RVC) zone as a possible functional interface between reflexive brainstem rhythms and volitional or affective control. By integrating comparative and connectomic perspectives, this review outlines how branchial motor circuitry may support a range of behaviors including airway protection, vocalization, and speech. Together, these observations suggest that the PPC may represent an anatomically strategic interface linking peripheral cranial nerve afferents with brainstem integrative networks involved in arousal and behavioral coordination. This framework provides a basis for future studies exploring how oropharyngeal sensory pathways interact with central neural circuits.
A semi-automated pipeline integrating ImageJ/Fiji and StarDist for the reproducible quantification of cellular and optical density metrics in immunofluorescence images of brain tissue.
Marques SI, Carmo H, Carvalho F … +2 more , Silva JP, Sá SI
Front Neuroanat · 2026 · PMID 41971975 · Full text
Quantitative immunofluorescence is widely used to assess molecular expression and cellular distribution across biological tissues, yet the analysis of large image datasets remains time-consuming and prone to user-depende...
Quantitative immunofluorescence is widely used to assess molecular expression and cellular distribution across biological tissues, yet the analysis of large image datasets remains time-consuming and prone to user-dependent variability. To address these limitations, we herein developed a semi-automated workflow that integrates ImageJ/Fiji for image processing, StarDist for nuclear segmentation, and spreadsheet- or Python-based routines for data curation. The pipeline standardizes critical analytical steps, including scale calibration, region-of-interest (ROI) definition, channel selection, and z-stack handling, while preserving essential metadata through a structured file-naming system. Optical density and cell-number metrics are exported automatically in a consistent format, enabling efficient consolidation into a unified dataset. Subsequent curation can be performed either manually in a spreadsheet software or fully automatically through custom Python scripts, allowing extraction of sample identifiers, regions, and markers, as well as calculation of normalized intensity values. Comparison with existing protocols proved that this workflow adheres to widely accepted quantification principles while markedly improving reproducibility, consistency, and analytical throughput. This method offers a straightforward, transparent, and scalable solution for fluorescence-based quantification suitable for laboratories with varying levels of computational expertise.
Correction: Unveiling the mechanisms of neuropathic pain suppression: perineural resiniferatoxin targets Trpv1 and beyond.
Shehab S, Javed H, Johnson AM … +3 more , Tariq S, Kumar CA, Emerald BS
Front Neuroanat · 2026 · PMID 41971974 · Full text
[This corrects the article DOI: 10.3389/fnana.2023.1306180.].
[This corrects the article DOI: 10.3389/fnana.2023.1306180.].
Justo Gonzalo (1910-1986): a pioneer of brain dynamics.
Gonzalo-Fonrodona I
Front Neuroanat · 2026 · PMID 41930219 · Full text
The present work offers an overview of the pioneering contributions of the neuroscientist Justo Gonzalo to the study of the human cerebral cortex, within the historical context of his time and in relation to current rese...
The present work offers an overview of the pioneering contributions of the neuroscientist Justo Gonzalo to the study of the human cerebral cortex, within the historical context of his time and in relation to current research. Gonzalo initially trained under Gonzalo Rodríguez Lafora (a disciple of Santiago Ramón y Cajal) and always maintained a close relationship with him and his circle, connecting him to the Spanish Neurological School (Cajal's school). He also trained in neurology in Austria and Germany (1933-1935). The research he called began during the Spanish Civil War (1936-1939) in a military hospital in Valencia, based on the study of patients with war-related brain injuries. Based on physiological criteria, Gonzalo described what he termed of the cortex: a multisensory and bilaterally symmetrical disorder caused by a unilateral parieto-occipital cortical lesion in an associative area. He brought to light singular perceptual phenomena, and was the first to study inverted or tilted perception (visual, tactile, and auditory), the improvement of perception through increased stimulus intensity or the presence of additional stimuli, as well as other phenomena that remain little known today. These findings and the study of different cortical syndromes led Gonzalo to propose that the specificity of brain functions is gradually distributed throughout the cerebral cortex, giving rise to cortical gradients, whose overlap would result in fairly nonspecific or multisensory adaptive regions. This unitary approach went beyond the rigid cortical parcellation for the anatomical localization of brain functions, and is closely aligned with current studies. The interpretation of the as analogous to the normal case, but with reduced excitability, led Gonzalo to apply scaling concepts that enabled him to develop formalizations and generalizations. He conducted this research in Spain, under very difficult conditions, with the support of the Cajal Institute. Despite the excellent international reception of his works in Spanish during the 1940s and 1950s, his contributions are scarcely known today due to the lack of timely publications in other languages. The publication of his works in English in 2023 has partially filled this gap.
Foxp2 mutations and abnormal brain and gastrointestinal development: insights from animal models of speech-language and autism spectrum disorders.
Fujita-Jimbo E, Kawahara G, Momoi T
Front Neuroanat · 2026 · PMID 41890637 · Full text
Autism spectrum disorder (ASD) and speech and language disorder (SLD) are distinct neurodevelopmental conditions, yet both share overlapping communication impairments. (), a key transcription factor involved in speech a...
Autism spectrum disorder (ASD) and speech and language disorder (SLD) are distinct neurodevelopmental conditions, yet both share overlapping communication impairments. (), a key transcription factor involved in speech and language development, harbors pathogenic mutations such as R553H, which cause SLD and have been suggested to contribute to aspects of ASD-related phenotypes. This review synthesizes insights from animal models to explore the molecular mechanisms by which mutations disrupt the development of the cerebral cortex, thalamus, and enteric nervous system. We highlight findings from heterozygous mutants and discuss severe phenotypes observed in homozygous mutants (2 and 2/mCherry-Tg mice), including profound ultrasonic vocalization deficits, brain malformations, and early lethality. Notably, these mice exhibit gastrointestinal abnormalities involving the epithelium, smooth muscle, and enteric nervous system, which are linked to impaired autoregulation and interference with Wnt signaling during development. Such observations underscore the relevance of the brain-gut-microbiome axis and Hirschsprung-like pathology in neurodevelopmental disorders. Finally, this review discusses future directions using gene-editing approaches in non-mammalian models-zebra finches, zebrafish, and -to dissect neural networks underlying intellectual disability and communication deficits. Collectively, these studies provide a framework for understanding -related molecular mechanisms in the pathogenesis of ASD and SLD.
Age-related dopaminergic integrity in the SNpc and VTA: morphometric and volumetric findings in marmoset ().
Azambuja MMO, de Santana NNM, Morais PLAG … +5 more , Vasiljevic GAM, Cavalcante JS, Bhagwandin A, Cavalcanti JRLP, Engelberth RC
Front Neuroanat · 2026 · PMID 41883691 · Full text
Given a convergence of evidence indicating age-related vulnerability in nuclei associated with basal ganglia circuits, understanding the pattern of normal aging in non-human primates is essential for basic and applied re...
Given a convergence of evidence indicating age-related vulnerability in nuclei associated with basal ganglia circuits, understanding the pattern of normal aging in non-human primates is essential for basic and applied research. To address this, we examined the age-dependent vulnerability of dopaminergic cells in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) of marmoset through morphoquantitative analysis of cytoarchitecture. Thus, we selected brain tissue from adult and aged marmosets processed for tyrosine hydroxylase (TH) immunohistochemistry. We estimated regional volume and counted TH-immunopositive (TH) neurons in the SNpc and VTA. Statistical comparisons used permutation tests and Spearman's tests to analyze differences between age groups. Although Spearman's correlation test showed a negative correlation between regional volume and age and between TH cell number and age, no significant differences were found in either the permutation test or Spearman's correlation for TH + neuronal number and for regional volume between the age groups for both nuclei. We concluded that aging in marmosets does not lead to significant loss of dopaminergic neurons or measurable volumetric reduction in the SNpc or VTA. Our results highlight the importance of understanding physiological aging in contrast to models characterized by structural degeneration, such as those found in pathological conditions. Understanding, in a promising experimental model as marmoset, the pattern of vulnerability and resilience of dopaminergic regions fills gaps in the literature and opens avenues for understanding molecular and functional changes related to aging.
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