Frontiers In Neuroanatomy[JOURNAL]
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200 papers
Prefrontal contributions to the executive control of visuospatial working memory across primate species.
Inger L, Hagan MA
Front Neuroanat · 2026 · PMID 41878494 · Full text
The ability to gain volitional control over our thoughts and actions to perform goal directed behaviors is largely owed to working memory (WM). WM is a highly distributed process requiring multiple integrated brain regio...
The ability to gain volitional control over our thoughts and actions to perform goal directed behaviors is largely owed to working memory (WM). WM is a highly distributed process requiring multiple integrated brain regions. The brain regions employed in WM are in part dependent on the sensory input to be remembered. For instance, visual and posterior parietal areas are critical for spatial WM. However, the prefrontal cortex (PFC) appears to be the node at which all of these brain regions converge on in WM, regardless of the sensory input. Understanding how the PFC has evolved to mediate spatial WM across primate species creates a powerful gateway to providing translational insight into human WM processing. This mini-review will discuss three key neuroanatomical regions of the PFC thought to be involved in the executive control of spatial WM - the dorsolateral prefrontal cortex (DLPFC), the ventrolateral prefrontal cortex (VLPFC), and the frontal eye fields (FEF). In particular, the review will focus on comparison of these regions between humans, macaques, and marmosets to determine the reliability of studying these WM brain regions across species.
Heterogeneity of astrocyte density, morphology and connexins in the mouse hippocampus.
Uelwer A, Sivakumar M, Umirdinov K … +5 more , Purath FFA, Oluma L, Anstötz M, von Gall C, Ali AAH
Front Neuroanat · 2026 · PMID 41878493 · Full text
The hippocampal formation is crucial for episodic learning and memory. In addition to neurons, astrocytes have also received increasing attention in recent years as essential components of brain networks by regulating th...
The hippocampal formation is crucial for episodic learning and memory. In addition to neurons, astrocytes have also received increasing attention in recent years as essential components of brain networks by regulating the blood-brain barrier, eliminating waste products via the glymphatic system, supporting neuronal activity by providing energy supply and metabolic substrates, and regulating extracellular neurotransmitter levels. Astrocytes are heterogeneous and highly dynamic cells that respond to neuronal activity and dysfunction via morphological and functional changes. Astrocytic connexins (Cx) 30 and 43 form the molecular basis for gap junctions and hemichannels and are, thus, central to coupling, intercellular communication and network integration of astrocytes in the brain. However, little is known about the spatial heterogeneity of astrocyte density, morphology and Cx expression in the subregions and layers of the hippocampus. Therefore, in this study, we used immunohistochemistry to analyze the density and detailed morphological features of astrocytes and the spatial distribution of Cx30 and Cx43 in the layers of CA1, CA3 and dentate gyrus (DG). Astrocyte density correlated positively with the intensity of Cx30- and Cx43-immunoreaction (Ir). The stratum lacunosum moleculare (SLM) of CA1 and CA3 and the subgranular zone (SGZ) of DG showed the highest density of GFAP-positive (+) astrocytes and the strongest Cx30- and Cx43-Ir. The GFAP+ astrocytic processes had the largest radial extent in the pyramidal layer of CA1 and CA3 and in the granular layer of the DG. Our study provides a comprehensive anatomical and comparative mapping of astrocytic density, morphology and Cx distribution in the mouse hippocampus and provides an important basis for further studies on the dynamics of neuron-glial interaction under different physiological and pathological conditions.
Postnatal expression of the transcription factor Ebf2 in motivation, reward, and pain-related circuits of the mouse brain.
Martínez-Estrada M, Cepeda-Varela MBD, Salinas-Villarreal AD … +7 more , Obregón-Fuentes MC, Real-Marín DA, Balderas-Díaz MA, Zomosa-Signoret V, Santana-Solano J, Santillán-Zerón M, Vidaltamayo R
Front Neuroanat · 2026 · PMID 41859334 · Full text
INTRODUCTION: Early B-cell factor 2 (Ebf2) is a transcription factor required for neuronal differentiation. However, its postnatal expression pattern and functional roles in the brain are not well characterized. This stu...
INTRODUCTION: Early B-cell factor 2 (Ebf2) is a transcription factor required for neuronal differentiation. However, its postnatal expression pattern and functional roles in the brain are not well characterized. This study examined the spatial distribution of Ebf2 in postnatal day 10 (P10) mouse brains and investigated its association with neural circuits mediating motivation, reward, and nociception. MATERIALS AND METHODS: Ebf2-TGFP transgenic mice, which express green fluorescent protein (GFP) as a reporter for Ebf2, were utilized. Immunofluorescence labeling and high-resolution microscopy were employed to visualize Ebf2 expression. Image data were analyzed using a deep learning-based segmentation pipeline for soma and axon identification. Three-dimensional reconstructions were registered to the Allen Brain Atlas. Quantitative comparisons between hemizygous and Ebf2-null mutant genotypes were conducted using linear mixed-effects models with Bonferroni and false discovery rate (FDR) corrections. RESULTS: Ebf2 expression was prominent in the dorsal diencephalic conduction system, including the septum, habenula, and interpeduncular nucleus. Ebf2 expression can also be detected in the lateral hypothalamic area, zona incerta, ventral tegmental area, and parabrachial nucleus. Expression was also detected in nociceptive and sensory-motor regions such as the periaqueductal gray, anterior pretectal nucleus, principal sensory nucleus of the trigeminal nerve, and superior colliculus. Ebf2-null mutant mice showed a significant reduction in Ebf2-TGFP cells across most of these regions. DISCUSSION: The results demonstrate that Ebf2 expression persists beyond embryonic development and is selectively enriched in neural circuits associated with motivation, reward processing, and nociceptive modulation. The marked reduction of Ebf2-TGFP expressing neurons in null mutants provides evidence for a postnatal requirement of Ebf2 in neuronal maintenance, rather than solely in early differentiation. Collectively, these findings broaden the functional scope of Ebf2 to include postnatal circuit stabilization and support its sustained regulatory role in brain systems that govern affective and pain-related behaviors.
Arterial supply of the interpeduncular part of the human oculomotor nerve.
Hajrović S, Bexheti E, Dožić A … +10 more , Bexheti S, Ćetković D, Marić Kujundžić H, Simić M, Milašinović S, Mirčić U, Vitošević Z, Milisavljević M, Mirčić A, Ćetković M
Front Neuroanat · 2026 · PMID 41852579 · Full text
The aim of this study was a detailed examination of the arterial vascularization of the interpeduncular cisternal part (ICP) of a proximal segment of the human oculomotor nerve (ON). The blood vessels of the ONs were car...
The aim of this study was a detailed examination of the arterial vascularization of the interpeduncular cisternal part (ICP) of a proximal segment of the human oculomotor nerve (ON). The blood vessels of the ONs were carefully microdissected and studied in 30 brain hemispheres using 6.3× to 20× magnification of the stereoscopic microscope. The arteries were injected with the mixture of 10% India ink and gelatin. For better understanding, one brainstem specimen was prepared following a histological procedure, transversely serially cut into 5-μm thick slices, and stained with Luxol fast blue. Another injected midbrain specimen was cut in 1-mm-thick transverse sections, completely cleared with methylsalycilate, and analyzed under transmitted light. The common oculomotor arteries (COAs) and the small oculomotor branches, which participate in the vascularization of the dorsal and ventral surfaces of the ICPs of ONs, were analyzed and their diameters were measured. The dorsal COA was present in 83.33% of the ONs, one per nerve, with an average diameter of 213.57 μm. The ventral COAs were found in 76.67% of the ONs, one per nerve, with an average diameter of 137.64 μm. The mean diameter of the dorsal COAs was significantly higher than the mean diameter of the ventral COAs ( < 0.001). The oculomotor fine central vessels supplied the oculomotor root exit zone (OREZ) with the central type of myelin, and distally, fascicles of the rest of ICS with the peripheral type of myelin. The results describing the ON arteries may have diagnostic and microsurgical significance. The lack of detailed morphological analysis of the dorsal region related to the ventral arterial vessels of the ICP, along with measurements of the oculomotor arterial diameters, guided us to conduct this anatomical research to improve diagnostic procedures and the quality of microsurgical interventions in this region.
Search for marker proteins to assess blood-brain barrier development.
Shigemoto-Mogami Y, Nakayama-Kitamura K, Sato K
Front Neuroanat · 2026 · PMID 41816640 · Full text
The blood-brain barrier (BBB) separates the central nervous system from the peripheral blood circulation, and performs various functions such as dictating central nervous system (CNS)-specific pharmacokinetics, and maint...
The blood-brain barrier (BBB) separates the central nervous system from the peripheral blood circulation, and performs various functions such as dictating central nervous system (CNS)-specific pharmacokinetics, and maintaining brain homeostasis. While previous studies have clarified the mechanisms underlying cerebrovascular network development, details regarding BBB maturation remain unknown. In this regard, we previously reported that the development of physical tightness of the BBB and the formation of perivascular glial structures begins on postnatal day 4 and is almost complete by postnatal day 15. Moreover, the difficulty in predicting BBB permeability has hindered the development of CNS drugs, and microphysiological systems (MPSs) that mimic the BBB have been extensively developed to address this issue. Building on this information, in this study, we examined the temporal expression patterns of vascular proteins (CD31, Tie2, CD34, CD146, and agrin), tight junction proteins (ZO-1, claudin-5, and occludin), transporters (P-gp, BCRP, and Glut1), and transferrin receptors (TfRs) during the postnatal period, along with the development of BBB tightness. Based on their temporal expression patterns, these proteins were divided into five groups. We selected representative proteins from groups 1-5, respectively, and examined the temporal expression changes to determine the developmental stage of the BBB. The expression patterns of these proteins can be used to determine the maturation stage of BBB-MPSs.
A novel methodology for localizing pallidal deep brain stimulation leads.
Pobiel B, O'Neill KJ, Patriat R … +12 more , Palnitkar T, Hill ME, Cole RC, Braun H, Alberico SL, Mohanty B, Bauer D, Park MC, Cooper SE, Vitek JL, Harel N, Aman JE
Front Neuroanat · 2026 · PMID 41809057 · Full text
INTRODUCTION: Positioning of deep brain stimulation (DBS) leads is paramount for optimizing therapeutic efficacy in Parkinson's disease (PD) and dystonia. Quantitative determination of lead position remains essential; ho...
INTRODUCTION: Positioning of deep brain stimulation (DBS) leads is paramount for optimizing therapeutic efficacy in Parkinson's disease (PD) and dystonia. Quantitative determination of lead position remains essential; however, current atlas-based targeting and stereotactic coordinate methods, while informative, limit patient specificity afforded by high-resolution reconstruction and introduce subjective variability. METHODS: We developed a novel pipeline in Unity™ to ingest 7T MRI-based reconstructions of DBS leads within the globus pallidus internus (GPi). Using anatomical landmarks and structure-specific algorithms, the GPi was parcellated into 12 anatomically-based subregions in a semi-automated, reproducible manner. Active contact positions were localized relative to a novel coordinate system developed from a GPi-based bounding box. A novel distance-to-border metric remapped contacts onto a common atlas (PD25) for population comparison against the same contacts mapped onto a common left GPi space using mid-commissural point (MCP) coordinates (Schaltenbrand-Wahren atlas). RESULTS: Fifteen leads from 10 PD subjects were used for ellipsoid fitting of active contact locations, resulting in an elliptical volume of 38.94 mm when using MCP coordinates, compared to a volume of 5.08 mm with our GPi-specific coordinates. The mean distance-to-ellipse centroid was 3.45 ± 1.57 mm for MCP coordinates and 2.03 ± 0.82 for our GPi-specific coordinates. Our distance-to-border remapping metric yielded mean adjustments of 0.81 mm (-axis) and 1.61 mm (-axis). A subset of six GPi active contacts were plotted with post-DBS motor improvement scores, demonstrating the ability to link lead location with clinical outcomes. CONCLUSION: Our novel software provides a quantifiable lead location with respect to the anatomical target, enhancing patient-specific lead localization by avoiding some of the pitfalls of either structure-to-atlas normalization or traditional stereotactic coordinates.
High-resolution imaging and three-dimensional model of the feline spinal cord.
Harnie J, Eddaoui O, Ashkar K … +7 more , Nadeau C, Mari S, Yassine S, Al Arab R, Audet J, Iorio-Morin C, Frigon A
Front Neuroanat · 2026 · PMID 41789255 · Full text
The spinal cord is a critical component of the central nervous system, responsible for integrating somatosensory inputs, generating motor outputs, and regulating autonomic functions. Despite its functional importance, hi...
The spinal cord is a critical component of the central nervous system, responsible for integrating somatosensory inputs, generating motor outputs, and regulating autonomic functions. Despite its functional importance, high-resolution anatomical data spanning from high cervical to sacral levels of the spinal cord remain largely unexplored, limiting our ability to develop accurate surgical strategies, computational models, and neuromodulation protocols. Here, we performed a segment-by-segment quantitative anatomical analysis of the feline spinal cord from C3 to S2 using histology and high-resolution micro-computed tomography (Micro-CT) to evaluate key structures including the dura mater, dorsal root ganglia, rootlets, and white and gray matter. We observed significant variability in dural thickness, as well as structured changes in rootlet orientation and density along the spinal axis. Dorsal root ganglia size, along with white and gray matter morphology, varied across spinal segments, with prominent enlargements at cervical and lumbar levels. Additionally, we constructed an open-access three-dimensional model by integrating magnetic resonance imaging (MRI), Micro-CT, and high-resolution Micro-CT data into a unified spatial reference. This model enables precise spatial analysis of spinal structures and facilitates advanced computational modeling of spinal cord function and neuromodulation strategies. Our results represent a valuable resource for anatomical, surgical, and bioengineering applications aimed at improving spinal interventions.
Differential morphology and distribution of GFAP astrocytes in vocal brain circuit in a songbird Southern house wren and humans.
Hinestroza-Morales S, López-Murillo C, Hoyos-Maya H … +4 more , Fernandez GJ, Villegas-Lanau A, Rivera-Gutierrez HF, Posada-Duque R
Front Neuroanat · 2026 · PMID 41726171 · Full text
Speech and song exhibit notable parallels between humans and birds. In humans, speech involves the Laryngeal Motor Cortex (LMC), Sensorimotor cortex (SMC), Broca's and Wernicke's areas, and the basal ganglia (striatum),...
Speech and song exhibit notable parallels between humans and birds. In humans, speech involves the Laryngeal Motor Cortex (LMC), Sensorimotor cortex (SMC), Broca's and Wernicke's areas, and the basal ganglia (striatum), which show convergent gene expression with avian song-control regions (RA, LMAN, HVC) and basal ganglia (Area X and medial striatum). While astrocyte morphology has been implicated in human speech, its role in song remains unknown. To compare astrocytes involved in speech and song, we evaluated cell density, astrocyte types, and their distribution in healthy humans and Southern house wrens using Nissl staining, GFAP and GS immunostaining, and 3D confocal imaging. The basal ganglia, human striatum and avian medial striatum, showed the highest cell density in both species. Human astrocyte distribution followed established cortical patterns, with enrichment in layers I-III and white matter (WM). In contrast, Southern house wrens exhibited restricted GFAP-positive astrocytes in vocal nuclei, with expression instead concentrated in telencephalic borders, vascular regions, and basal ganglia WM. Astrocyte morphology varied regionally in both species; basal ganglia astrocytes were especially complex, yet Southern house wrens exhibited reduced branching even after normalizing for brain volume/body weight ratio, indicating species-specific differences in complexity. GS-positive astrocytes were abundant and homogeneous throughout the pallium, including all vocal nuclei, unlike the more restricted GFAP-positive subset. Cross-species analysis of public songbird datasets confirmed minimal and strong (GS gene) expression in telencephalic astrocytes, opposite to humans, who show robust expression of both markers. Overall, GS astrocytes displayed a broadly uniform organization in both species, whereas GFAP astrocytes exhibited more restricted and enriched distributions, particularly in human speech-related basal ganglia, revealing species-specific differences in astrocyte architecture within vocal circuits.
Editorial: Decoding the neuroanatomy of addiction: insights into substance use disorders.
Mitrano DA, Robishaw JD
Front Neuroanat · 2026 · PMID 41710725 · Full text
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Commentary: The amygdaloid body of the family Delphinidae: a morphological study of its central nucleus through calbindin-D28k.
de Souza LC, Morais PLAG, Bhagwandin A … +1 more , Cavalcanti JRLP
Front Neuroanat · 2026 · PMID 41657723 · Full text
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Mouse spinal cord cellular mapping of dopamine D2 receptors-containing cells.
Tarot P, Cutando L, Castell L … +2 more , Puighermanal E, Valjent E
Front Neuroanat · 2025 · PMID 41640717 · Full text
The spinal cord (SC) serves as the primary relay for sensory information originating in the periphery and transmitted to the brain for processing. Sensitive primary afferent fibers project to the dorsal horn, which conta...
The spinal cord (SC) serves as the primary relay for sensory information originating in the periphery and transmitted to the brain for processing. Sensitive primary afferent fibers project to the dorsal horn, which contains a highly diverse array of neurons forming a complex network of excitatory and inhibitory circuits. Previous studies have indicated that this neuronal network can be modulated by the monoaminergic system, particularly through the spinal dopaminergic circuit, partly via dopamine D2 receptors (D2R). However, the identity of the cells expressing D2R within the spinal cord remains largely unknown. By combining whole-mount immunostaining, volume imaging and Ribotag methodology, we analyzed the distribution and characterized the molecular identity of D2R-expressing cells of the mouse spinal cord. Our study revealed that D2R are expressed by neurons, but not glial cells, distributed preferentially in the dorsal horn of the spinal cord. Furthermore, SC D2R neurons were not motorneurons but instead belong to molecularly distinct classes of excitatory and inhibitory neuronal populations. By providing a detailed molecular characterization of D2R-expressing cells in the spinal cord, the present work lays the foundation for more targeted investigations into the specific functional roles of D2Rs in sensory information processing.
Cortical white matter: no longer a silent partner.
Rockland KS, Rushmore RJ
Front Neuroanat · 2025 · PMID 41552372 · Full text
This takes the position that the cell-sparse cortical white matter (WM) of gyrencephalic brains has too long held a secondary place in neuroanatomical investigations of cell-dense gray matter (GM) regions. This is unjust...
This takes the position that the cell-sparse cortical white matter (WM) of gyrencephalic brains has too long held a secondary place in neuroanatomical investigations of cell-dense gray matter (GM) regions. This is unjustified and even problematic because WM, like GM, has its own subcellular, cellular, and supracellular multi-scale organization. Axons are not passive cables or wires, but engage in multiple processes, some in cooperation with neurons in the GM and, as increasingly recognized, also inter- and intra-axonal. In five sections of this review, we revisit traditional assumptions about WM organization and touch on recent results regarding: the axonal cytoskeleton and myelination, neuroanatomical approaches to global WM organization, open issues about "endpoints" (i.e., origin and termination of axon bundles), and orderly vs. "scrambled" topographies. There has been significant research progress at all spatial scales, and there is good reason to anticipate a more holistic approach in the next stages that will bring WM investigations more in line with the integrative approaches already customary in GM investigations.
Marmoset superior colliculus: neuronal expression of somatostatin but not vasoactive intestinal peptide or neuropeptide Y.
Chong MHY, Cho EKL, Rosa MGP … +1 more , Atapour N
Front Neuroanat · 2025 · PMID 41458172 · Full text
The superior colliculus (SC) is a layered midbrain structure that plays a crucial role in integrating sensory information toward functions such as directing eye and head movements. Despite significant literature on its a...
The superior colliculus (SC) is a layered midbrain structure that plays a crucial role in integrating sensory information toward functions such as directing eye and head movements. Despite significant literature on its anatomical structure and connections, there are still important gaps in our knowledge of the diversity of cell types, particularly in primates. Here, using immunostaining, we examined the expression of three different neuropeptides [somatostatin (SST), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY)] in the SC of adult marmoset monkeys (). We found neurons expressing SST (SST-positive, SST+) across all cellular layers of the SC, which corresponded to approximately 3-5% of the total neuronal population in this structure. SST+ neuronal density as estimated by stereological sampling methods was about 3,140/mm in the top layer, stratum griseum superficiale (SGS) and decreased across the dorsoventral axis, roughly in line with the overall neuronal density estimated from NeuN stained nuclei. Co-staining of SST with gamma-aminobutyric acid (GABA), confirmed the inhibitory nature of these cells. However, we found no evidence of VIP- or NPY-positive neurons in the marmoset SC, despite the presence of clearly stained neurons in other structures, in the same sections. Our data adds to the understanding of neuronal diversity of SC in primates and provides quantitative estimates of SST+ neurons in this structure that is essential for better understanding of its function and phylogeny.
Functional neuroanatomy of dopaminergic arousal systems: implications for the wake-promoting effect of psychostimulants, with particular reference to modafinil.
Szabadi E
Front Neuroanat · 2025 · PMID 41445539 · Full text
Arousal involves activation of the cerebral cortex by inputs from subcortical (hypothalamic, brainstem) wake-promoting nuclei, utilizing monoamine (noradrenaline, dopamine, serotonin, histamine) and neuropeptide (orexin)...
Arousal involves activation of the cerebral cortex by inputs from subcortical (hypothalamic, brainstem) wake-promoting nuclei, utilizing monoamine (noradrenaline, dopamine, serotonin, histamine) and neuropeptide (orexin) neurotransmitters. Dopaminergic neurones of the midbrain, originating from distinct nuclei [pars compacta of substantia nigra (SNc), ventral tegmental area (VTA), and other clusters of dopaminergic neurones in the ventral periaqueductal gray (vPAG)] and the pontine dorsal raphe nucleus (DRN), constitute a powerful wake-promoting system. Cortical activation by dopaminergic neurones can be due to either direct projections from the VTA and vPAG/DRN, to the cerebral cortex, or indirect projections from the VTA via the nucleus accumbens (NAc)/ventral pallidum (VP) and from the SNc via the thalamus. Stimulation of the VP, by inputs from the VTA via the NAc, can activate wake-promoting noradrenergic and orexinergic neurones, and stimulation of the thalamus, by inputs from the SNc, can activate wake-promoting glutamatergic thalamocortical neurones. There is also a two-way mutually reinforcing connection between the VTA/NAc/VP and SNc/thalamus systems, indicating the key role of the NAc in dopaminergic arousal regulation. Dopaminergic psychostimulants (e.g., amphetamine, cocaine) are highly addictive drugs of abuse, that activate both reinforcement mechanisms and promote wakefulness, by enhancing dopaminergic neurotransmission. The addictive potential of psychostimulants is related to the stimulation of reinforcement processes. Modafinil, an atypical psychostimulant, enhances wakefulness without affecting reinforcement, and thus is devoid of addictive potential. Unraveling the mode of action of modafinil may give insight into the neural mechanisms controlling reinforcement and arousal. Recent evidence indicates that the powerful arousal-enhancing effect of psychostimulants may mainly be due to indirect cortical activation via the NAc and thalamus.
Cajal's organization of neuronal nucleus revisited.
Lafarga M, Berciano MT, Narcís JO … +2 more , Baltanás FC, Tapia O
Front Neuroanat · 2025 · PMID 41415602 · Full text
In 1906, Cajal was awarded the Nobel Prize in Physiology or Medicine for his pioneering studies on the structure and organization of nerve centers. Notably, in 1910, Cajal published a seminal work in which he described t...
In 1906, Cajal was awarded the Nobel Prize in Physiology or Medicine for his pioneering studies on the structure and organization of nerve centers. Notably, in 1910, Cajal published a seminal work in which he described the essential components of the neuronal nucleus, primarily using his reduced silver nitrate procedure. Using modern microscopy techniques, we have identified the current equivalents of the structures originally described by Cajal. These include the "fibrillar center-dense fibrillar component units" of the nucleolus, "nuclear speckles," "transcription factories," and "the Cajal body." Importantly, these structures represent key nuclear compartments involved in the transcription of rDNA and protein-coding genes, pre-rRNA and pre-mRNA processing and spatial genome organization. Most of the nuclear components described by Cajal are now recognized as dynamic "nuclear condensates" assembled through liquid-liquid phase separation mechanisms that depend on various categories of RNA and RNA-binding proteins.
Transmitter and ion channel profiles of saccadic omnipause neurons and cholinergic non-omnipause neurons in human nucleus raphe interpositus.
Mayadali ÜS, John M, Abspacher M … +3 more , Schmitz C, Shaikh AG, Horn AKE
Front Neuroanat · 2025 · PMID 41403854 · Full text
BACKGROUND: Omnipause neurons (OPN) are glycinergic neurons that tonically inhibit burst neurons between saccades. In primates, OPNs are located bilaterally around the midline at the level of the traversing rootlets of t...
BACKGROUND: Omnipause neurons (OPN) are glycinergic neurons that tonically inhibit burst neurons between saccades. In primates, OPNs are located bilaterally around the midline at the level of the traversing rootlets of the abducens nerve in the pontine brainstem forming the nucleus raphe interpositus (RIP). Healthy OPNs are previously characterized by dense perineuronal net (PN) ensheathment, parvalbumin (PAV) and voltage-gated potassium channel Kv1.1 and Kv3.1 expression. MOTIVATION: The ion channel and transmitter profile of OPNs in human has not been established. The further characterization of OPNs should allow for local delineation of OPNs from other types of neurons found in RIP, as well as identifying potential markers for eye movement disorders such as opsoclonus myoclonus syndrome. METHODS: Double immunoperoxidase based-stainings of transverse pontine sections containing human RIP for aggrecan (ACAN) and non-phosphorylated neurofilaments (SMI32) was used to identify OPNs. In consecutive thin paraffin sections, stainings using antibodies against low voltage-activated ion channels (HCN, Cav3) and transmitter related proteins were performed. RESULTS: A separate but morphologically similar population to OPNs was identified around the midline at the same level as OPNs in human pontine sections. This population was cholinergic, lacked PNs, but was labeled by SMI32. Further examination revealed that OPNs and cholinergic non-OPN populations differ in their ion channel (Kv3.1, HCN1-2, Cav3.2) and transmitter related protein (GABRA, GAD, GlyR, vGlut, GluR) expression. CONCLUSION: OPNs and cholinergic non-OPNs are located intermingled within the traditionally identified RIP, however they expressed distinct histochemical signatures from OPNs. Although the functional significance of the cholinergic non-OPN population in human brainstem is unclear, these findings suggest important distinguishing features that could be missed in histopathological examinations of post-mortem cases with saccadic disorders.
Developmental and adult expression of the Meis2 transcription factor in the central nervous system of : a developmental and evolutive analysis.
Morona R, Martinez A, Moreno N
Front Neuroanat · 2025 · PMID 41280242 · Full text
Myeloid ecotropic viral integration site 2 (Meis2) is a three-amino-acid-loop-extension (TALE) transcription factor (TF) involved in key neurodevelopmental processes, such as neuronal differentiation and brain regionaliz...
Myeloid ecotropic viral integration site 2 (Meis2) is a three-amino-acid-loop-extension (TALE) transcription factor (TF) involved in key neurodevelopmental processes, such as neuronal differentiation and brain regionalization. Its expression is well documented in amniotes and teleosts, but its distribution in the developing brain of anamniote tetrapods remains poorly understood. Therefore, the distribution of Meis2-immunoreactive (-ir) cells was analyzed throughout the developmental stages of the brain, revealing a dynamic, stage-specific expression pattern. From the early embryonic stages, Meis2-ir cells were found in the telencephalon, specifically in the ventrolateral pallium and subpallium; the diencephalon, particularly in the prosomere 3 and transiently in p2 and in the habenula; the optic tectum; the mesencephalic tegmentum; and the rhombencephalon. During the premetamorphic stages, Meis2 expression extended rostrally in the olfactory bulb (OB) and to subpallial derivatives, including scattered cells in the amygdaloid region. It was present in the alar and basal hypothalamus. During the metamorphic climax and juvenile phases, Meis2-ir expression became clearly defined in specific mature nuclei, specifically in the ventral pallium, the bed nucleus of the stria terminalis, septal nuclei, supra-paraventricular and mammillary hypothalamus, and prethalamic nuclei. In addition, from the metamorphic climax stages, Meis2 occupied a number of tectal layers and was observed in the cerebellar nucleus. The most prominent and constant expression was observed in the rhombencephalon, particularly in areas surrounding the isthmus and the reticular formation. This expression extended from rostral rhombomeres (r1-r3) caudally into the lateral line system and raphe nuclei. These results highlight the conserved and temporally regulated role of Meis2 in the regional specification and maturation of the central nervous system and reveal particularities related to cell specification.
Spinal cord morphology and PKD2L1 cells distribution: effects of age, sex, and spinal segment in mice.
Leblond L, Ramirez-Franco J, Michelle C … +2 more , Wanaverbecq N, Evin M
Front Neuroanat · 2025 · PMID 41210889 · Full text
INTRODUCTION: Morphometrical studies of the mouse spinal cord are often limited to one age or sex, restricting our understanding of anatomical variability. This study provides a detailed analysis of the spinal cord in mi...
INTRODUCTION: Morphometrical studies of the mouse spinal cord are often limited to one age or sex, restricting our understanding of anatomical variability. This study provides a detailed analysis of the spinal cord in mice, examining the effects of age, sex, and spinal region, along with the distribution of PKD2L1-positive (PKD2L1) cells along the rostro-caudal axis. METHODS: Using 811 transverse sections from a total of 18 3- and 8-week-old mice, DAPI immunofluorescence and confocal imaging, 14 dimensions of gray matter (GM), white matter (WM), and the central canal (CC) were assessed using landmarks positioning and segmentation methods. RESULTS: Age was the most influential factor: between 3- and 8- weeks-old, the spinal cord showed reduced rostro-caudal length ( = 2.49e-04), smaller ventral GM horns ( < 0.005), deeper ventral commissures ( = 5.58e-13), and an increase in CC area (from 1925.58 ± 630.16 μm to 2199.50 ± 569.44 μm). Looking at sex-related differences, females showed higher variability across several parameters, with subtle differences in GM organization ( < 0.05) and CC morphology (mean area = 2146.39 ± 632.91 μm in females vs. 1998.36 ± 589.85 μm in males). Along the rostro-caudal axis, WM size, as well as GM dorsal and ventral horn dimensions, differed significantly across spinal segments ( < 0.005). CC position also shifted dorsally in cervical and lumbar regions depending on age and sex ( < 0.005). PKD2L1 cells were mainly clustered near the CC, with over 46% located proximally. The highest densities (>300 cells/segment) were found in lumbar and lower thoracic regions. DISCUSSION: These results indicate progressive structural changes during development, including reorganization of cells and CC architecture stabilization. The distribution of PKD2L1 cells is consistent with their proposed role as cerebrospinal fluid-contacting neurons potentially involved in sensing fluid composition and modulating locomotor control. Their increased presence in caudal segments suggests functional specialization in different spinal regions. CONCLUSION: This work provides detailed, segment-specific anatomical data crucial for developing accurate and physiological numerical models. Adding age and sex differences emphasizes the need to reflect biological variability in simulations. Additionally, the mapping of PKD2L1 neurons offers valuable insight into their spatial organization and potential involvement in sensory processing, locomotor function, and neurological or developmental disorders.
The extracellular matrix in peripheral nerve repair and regeneration: a narrative review of its role and therapeutic potential.
Metafune M, Muratori L, Fregnan F … +2 more , Ronchi G, Raimondo S
Front Neuroanat · 2025 · PMID 41194908 · Full text
The extracellular matrix (ECM) is a non-cellular and gelatinous component of tissues, rich in proteins and proteoglycans, that provides information about the environment, forms a reservoir of trophic factors and regulate...
The extracellular matrix (ECM) is a non-cellular and gelatinous component of tissues, rich in proteins and proteoglycans, that provides information about the environment, forms a reservoir of trophic factors and regulates cell behavior by binding and activating cell surface receptors. This important network acts as a scaffold for tissues and organs throughout the body, playing an essential role in their structural and functional integrity. It is essential for cells to connect and communicate with each other and play an active role in intracellular signaling. Due to these properties, in recent decades the potential of the extracellular matrix in tissue engineering has begun to be explored with the aim of developing innovative biomaterials to be used in regenerative medicine. This review will first outline the components of the extracellular matrix in the peripheral nerve, followed by an exploration of its role in the regeneration process after injury, with a focus on the mechanisms underlying its interactions with nerve cells. Qualitative and quantitative methods used for extracellular matrix analysis will be described, and finally an overview will be given of recent advances in nerve repair strategies that exploit the potential of the extracellular matrix to enhance regeneration, highlighting the critical issues of extracellular matrix molecule use and proposing new directions for future research.
Vascular degeneration and retinal remodeling in rd10 mice: correlating OCT, OCTA, and histological findings.
Albertos-Arranz H, Sánchez-Sáez X, Kutsyr O … +4 more , Fernández-Sánchez L, Sánchez-Castillo C, Lax P, Cuenca N
Front Neuroanat · 2025 · PMID 41194907 · Full text
INTRODUCTION: Identifying long-term changes in retinal structure and vasculature is essential for interpreting imaging techniques such as optical coherence tomography (OCT) and OCT angiography (OCTA) in retinal diseases...
INTRODUCTION: Identifying long-term changes in retinal structure and vasculature is essential for interpreting imaging techniques such as optical coherence tomography (OCT) and OCT angiography (OCTA) in retinal diseases. We characterized long-term alterations in vasculature, retinal structure, and glial cells by combining immunohistochemistry (IHC) with OCT and OCTA in a murine model of retinitis pigmentosa. METHODS: Transversal retinal sections and wholemount retinas from C57BL/6J and rd10 mice, aged P20 to 24 months, were immunostained to evaluate retinal structure, glial cells, retinal pigment epithelium (RPE), and the vascular network. OCT and OCTA images from the central retina were also analyzed. RESULTS: Significant retinal remodeling in the inner retina occurs over time and was detectable from 4 months using IHC and from 6 months using OCT. Remodeling was characterized by glial activation (reactive gliosis) and the formation of hyperreflective columns, which contain Müller cells, activated microglia, RPE, and choroidal vessels in the late stages. No significant differences were observed between OCTA and IHC vascular density of the superficial vascular plexus (SVP) and deep capillary plexus (DCP) in rd10 mice at any time points, except at 2 months (SVP, = 0.009; DCP, = 0.001). This seems a critical stage, suggesting differing rates of blood flow reduction and structural vessel loss. A peak of vascular degeneration in the SVP of rd10 mice was detected by OCTA between 2 and 6 months ( = 0.003), but not by IHC. Vascular degeneration peak of DCP in rd10 was observed between P20 and 2 months using OCTA ( < 0.0001), and between 2 and 6 months using IHC ( = 0.003). CONCLUSION: Overall, OCTA and IHC yielded comparable long-term vascular density results, supporting OCTA as a reliable, non-invasive tool for studying vessel degeneration in animal models. Therefore, longitudinal evaluation of retinal remodeling through OCT and OCTA constitutes a valuable methodology for investigating disease mechanisms and guiding therapeutic development.
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