Frontiers In Neuroanatomy[JOURNAL]
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200 papers
Multi-neuromeric origin of tyrosine hydroxylase-positive neurons within the substantia nigra and ventral tegmental area.
Ferran JL, Lucero-Arteaga F, Ayad A … +5 more , Kutsenko Y, Alonso A, Do-Couto BR, García-Cabezas MÁ, Tseng KY
Front Neuroanat · 2025 · PMID 40519251 · Full text
During early developmental stages, the brain is divided into three primary regions: the forebrain (prosencephalon), the hindbrain (rhombencephalon), and the spinal cord. These regions are further segmented into transvers...
During early developmental stages, the brain is divided into three primary regions: the forebrain (prosencephalon), the hindbrain (rhombencephalon), and the spinal cord. These regions are further segmented into transverse units called neuromeres, each with distinct molecular identities that guide their specialization through development. Such modular organization is evolutionarily conserved and shapes the structural and functional complexity of the brain. The substantia nigra (SN) and ventral tegmental area (VTA) are key midbrain regions involved in reward, motivation, and motor control. They contain dopamine-producing tyrosine hydroxylase (TH)-positive neurons, which are historically classified into three anatomical groups-A8 (retrorubral field), A9 (SN pars compacta), and A10 (VTA)-each with distinct anatomical and functional properties. Recent studies revealed further sub-regional organization along medial-lateral and anterior-posterior gradients, suggesting specialized roles tied to their developmental origins. This study uses the prosomeric framework to map the segmental distribution of TH-positive neurons within the SN and VTA across different mammalian species and developmental stages. Using a comparative analysis of rodent, non-human primate and human specimens, we were able to demonstrate that TH-positive neurons within the SN and VTA exhibit a multi-neuromeric organization, with neuronal populations distributed across the diencephalic prosomeres (dp1-dp3), the midbrain prosomeres (mp1-mp2) and the isthmic rhombomere (r0). It is therefore conceivable that such multi-neuromeric origin of TH-positive neurons within the SN and VTA likely influence the patterns of connectivity and functional specialization of the dopamine system.
Two patterns in apical dendrite extensions of projection neurons within cerebral cortex of reeler mutant mice.
Ichikawa R
Front Neuroanat · 2025 · PMID 40519250 · Full text
INTRODUCTION: Pyramidal-like projection neurons in the cerebral cortex exhibit layer-specific positioning of their cell bodies and target specific cortical regions with their apical dendrites. Reeler mutant mice, which l...
INTRODUCTION: Pyramidal-like projection neurons in the cerebral cortex exhibit layer-specific positioning of their cell bodies and target specific cortical regions with their apical dendrites. Reeler mutant mice, which lack the gene for the reelin protein gene secreted by Cajal-Retzius cells and have their projection neurons scattered throughout the cortex, display relatively intact global and local neuronal network connections compared with wild-type mice. The irregular morphologies of these cells, which extend their apical dendrites in a neuron-disoriented direction, are thought to compensate for the malposition of the neurons. I aimed to investigate the projection target-specific regulation of this apical dendrite extension pattern in reeler mice. METHODS: To this end, three types of projection neurons-corticospinal (CS), corticothalamic (CT), and corticocallosal (CC) neurons-were evaluated using retrograde labeling techniques. RESULTS AND DISCUSSION: Reeler CS neurons displayed a congregation pattern of apical dendritic terminal tips in a specific upper cortical zone, whereas reeler CC neurons exhibited a dispersed pattern of scattered tips throughout the cortex. However, reeler CT neurons showed a hybrid pattern, exhibiting characteristics of both congregation- and dispersion-type neurons. Moreover, apical dendrite extension of these projection neurons follows either a congregation or dispersion mode from postnatal day 0 (P0), which subsequently defines their terminal tip positioning by P8. Thus, this early patterning of apical dendrite arborization in reeler projection neurons likely contributes to the formation of projection target-specific neuronal connections during the first two postnatal weeks.
High-resolution segmentation of the cavum septum pellucidum in young adult human brains.
Rios A, Alier A, Aneja M … +10 more , Nimeri F, Lavery K, Fisher J, Wiyathunge R, Kubicki M, Yeterian E, Bouix S, Makris N, Arciniega H, Rushmore RJ
Front Neuroanat · 2025 · PMID 40464003 · Full text
The cavum septum pellucidum (CSP) is a small cerebrospinal fluid-filled space found between the lateral ventricles of the forebrain that is often used as a biomarker for neurological disease and brain injury. The inciden...
The cavum septum pellucidum (CSP) is a small cerebrospinal fluid-filled space found between the lateral ventricles of the forebrain that is often used as a biomarker for neurological disease and brain injury. The incidence of the CSP varies widely in different studies, with many reports finding that the CSP is frequently absent in healthy brains. Variables such as race, age and sex are typically not well-reported in CSP studies, presenting a challenge to understanding the normal distribution of the CSP in adult human brains. Moreover, the small size and frequently indistinct borders present a challenge for automated segmentation of the CSP. To address these issues, we developed a novel manual parcelation approach to volumetrically segment the CSP in high-resolution T1-weighted structural MRIs from male and female participants in the young adult dataset of the Human Connectome Project (HCP). We identified the CSP in 95.6% of subjects, compared to 57.1% when the automated segmentation approach was used on the same subjects. The CSP volume was significantly larger in male than female brains, both in terms of raw volume and volumes normalized for intracranial volume. To our knowledge, this study is the first to develop and validate a segmentation protocol for CSP volume, and to evaluate both the incidence and volume of the CSP in a representative population of young adults. Overall, these results provide a more accurate representation of the CSP in control populations, laying an improved foundation for its potential use as a biomarker for various disorders.
The meningo-orbital band from an endoscopic transorbital approach: an anatomical study.
Manfrellotti R, Gagliano D, Costanzo R … +9 more , Mosteiro A, Codes Méndez M, Perera Valdivia D, Lasunin N, Giussani CG, Carrabba GG, Enseñat J, Di Somma A, Prats-Galino A
Front Neuroanat · 2025 · PMID 40438257 · Full text
INTRODUCTION: The meningo-orbital band (MOB) is an intricate dural structure extending between the periorbita, the frontal dura, and the temporal dura. The endoscopic transorbital approach (ETOA) provides a more thorough...
INTRODUCTION: The meningo-orbital band (MOB) is an intricate dural structure extending between the periorbita, the frontal dura, and the temporal dura. The endoscopic transorbital approach (ETOA) provides a more thorough understanding of its anatomy. MATERIALS AND METHODS: Anatomical dissections were performed on 15 human head specimens (30 orbits) at the Laboratory of Surgical Neuroanatomy (LSNA) at the University of Barcelona. The specimens were preserved using a Cambridge solution for optimal fixation. An endoscopic transorbital approach (ETOA) was used to isolate the meningo-orbital band (MOB). A rigid 4-mm endoscope with an HD camera and light source was used for the procedure. Multislice helical CT scans were performed both before and after the dissections to document the anatomical features. Additionally, a specialized software (The ImagingSource®) was used to calculate the variability in the angle between the first two bone pillars of the ETOA: the sagittal crest (SC) and the lesser sphenoid wing (LSW). The vascularization of the MOB was studied by longitudinally cutting the band and using red and blue latex injections into the carotid arteries and jugular veins, respectively, to highlight the cerebral vasculature. RESULTS: In the endoscopic transorbital approach (ETOA), key structures, including the greater and lesser sphenoid wings, are excised, exposing the meningo-orbital band (MOB). The MOB extends from the periorbita medially to the frontal and temporal dura laterally and is firmly attached to the anterior clinoid process (ACP). Anatomical dissection reveals the MOB's complex three-dimensional structure and its relationships with cranial nerves III, IV, and V1 along the lateral wall of the cavernous sinus and the superior orbital fissure (SOF). The ACP serves as a protective barrier between the MOB and the paraclinoid segment of the internal carotid artery (ICA). Additionally, the MOB is vascularized by the MOB artery (MOBA), a branch of the middle meningeal artery, which bifurcates into the frontal and temporal branches. CONCLUSION: This study highlights the key anatomical relationships of the meningo-orbital band (MOB) with critical structures, including cranial nerves III, IV, and V1, as well as the ICA. These findings are essential for refining surgical planning and improving the safety and precision of skull base surgery.
Editorial: Editors' showcase: frontiers in neuroanatomy.
DeFelipe J, Lübke JHR
Front Neuroanat · 2025 · PMID 40432713 · Full text
Abstract loading — click title to view on PubMed.
Chronic silencing of Drd1a-Cre+ neurons impairs dopaminergic-driven cortical activation.
Messore LF, Vadisiute A, Edmead H … +6 more , Durmaz A, Abuelem M, Chedotal F, Hoerder-Suabedissen A, Mann EO, Molnár Z
Front Neuroanat · 2025 · PMID 40357372 · Full text
In the somatosensory cortex of transgenic mice, Cre-recombinase is expressed under the control of the dopamine receptor D1 (Drd1a) promoter in lower layer 6. These neurons selectively project to the higher-order thalamic...
In the somatosensory cortex of transgenic mice, Cre-recombinase is expressed under the control of the dopamine receptor D1 (Drd1a) promoter in lower layer 6. These neurons selectively project to the higher-order thalamic nuclei and participate in the cortico-thalamo-cortical loops involved in sensory processing and stimulus representation. However, the role of dopaminergic modulation in activating this neuronal population during cortical arousal remains poorly understood. In this study, we examined the effects of D1 (SKF-81297) and D2 (Quinpirole) receptor agonists on cortical network activation. We further investigated the consequences of silencing these neurons using a Snap25 conditional knockout mouse model. We report a decrease in cellular and neuronal density in the subplate/L6b with normal development from P8 to adulthood. Conversely, the density of Drd1a-Cre+ neurons goes up in Snap25 cKO brains when comparing the same ages. Moreover, we observe that silencing of Drd1a-Cre+ neurons has no effect on microglial cells. Our results demonstrate that both D1 and D2 agonists require the Drd1a-Cre+ neurons to modulate cortical activity effectively. Our study provides new insights into the fundamental role of Drd1a-Cre+ neurons in cortical activation and sensory processing.
Parvalbumin interneurons in the hippocampal formation of individuals with Alzheimer's disease: a neuropathological study of abnormal phosphorylated tau in neurons.
Merino-Serrais P, Plaza-Alonso S, Tapia-Gonzalez S … +2 more , León-Espinosa G, DeFelipe J
Front Neuroanat · 2025 · PMID 40275866 · Full text
Alzheimer's disease (AD) is the most common neurodegenerative disorder in the elderly. Recent efforts have centered on understanding early events that trigger AD, aiming to facilitate early diagnosis and intervention for...
Alzheimer's disease (AD) is the most common neurodegenerative disorder in the elderly. Recent efforts have centered on understanding early events that trigger AD, aiming to facilitate early diagnosis and intervention for improved patient outcomes. The traditional histopathological features observed in AD encompass the extracellular accumulation of amyloid-beta protein and the intracellular abnormal phosphorylation of Tau protein (pTau). However, elucidating how these pathological hallmarks ultimately contribute to cognitive deficits remains a complex challenge. While AD is commonly conceptualized as a disorder characterized by synaptic failure, substantial knowledge gaps persist regarding the mechanisms underlying the onset and progression of the disease, underscoring the need for novel and more effective therapeutic approaches. In this context, the impairment of GABAergic paravalbumin (PV+) neurons has been proposed as a crucial factor contributing to neuronal network dysfunction and cognitive decline in AD. The presence of pTau in pyramidal neurons is directly linked to their impairment in AD; however, the effect of pTau in PV+ neurons remains unclear. In this present study, we analyzed the existence of PV+ neurons containing pTau using immunocytochemistry in the hippocampal formation and entorhinal cortex of human samples from diagnosed AD cases and individuals without neurological or psychiatric disorders. Two pTau isoforms, pTau and pTau, corresponding to early and late stages of AD respectively, were examined. Our findings indicate that most PV+ neurons across the hippocampal formation and entorhinal cortex did not contain pTau in either group cases. Interestingly, while AD cases diagnosed with dementia exhibited a higher number of pTau+ neurons, the majority of PV+/pTau+ neurons were found in individuals with no neurological alterations. This suggests that the presence of pTau in PV+ neurons does not directly correlate with the overall abundance of pTau+ neurons. Given that PV+ neuron impairment is a key pathogenic mechanism in AD and is associated with cognitive decline, understanding the changes in PV+ neurons during AD progression could provide critical insights into the alterations of neuronal circuits underlying the disease.
Sœmmerring's error: the root of the story. The C8 nerve is a misconception. A historical review and anatomical perspectives.
Chaynes P, Carfagna L, Poinsignon M … +1 more , De Barros A
Front Neuroanat · 2025 · PMID 40275865 · Full text
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Contrasting patterns of extrasynaptic NMDAR-GluN2B expression in macaque subgenual cingulate and dorsolateral prefrontal cortices.
Joyce MKP, Datta D, Arellano JI … +4 more , Duque A, Morozov YM, Morrison JH, Arnsten AFT
Front Neuroanat · 2025 · PMID 40255911 · Full text
Expression of the N-methyl-D-aspartate receptor, particularly when containing the GluN2B subunit (NMDAR-GluN2B), varies across the prefrontal cortex (PFC). In humans, the subgenual cingulate cortex (SGC) contains among t...
Expression of the N-methyl-D-aspartate receptor, particularly when containing the GluN2B subunit (NMDAR-GluN2B), varies across the prefrontal cortex (PFC). In humans, the subgenual cingulate cortex (SGC) contains among the highest levels of NMDAR-GluN2B expression, while the dorsolateral prefrontal cortex (dlPFC) exhibits a more moderate level of NMDAR-GluN2B expression. NMDAR-GluN2B are commonly associated with ionotropic synaptic function and plasticity and are essential to the neurotransmission underlying working memory in the macaque dlPFC in the layer III circuits, which in humans are afflicted in schizophrenia. However, NMDAR-GluN2B can also be found at extrasynaptic sites, where they may trigger distinct events, including some linked to neurodegenerative processes. The SGC is an early site of tau pathology in sporadic Alzheimer's disease (sAD), which mirrors its high NMDAR-GluN2B expression. Additionally, the SGC is hyperactive in depression, which can be treated with NMDAR antagonists. Given the clinical relevance of NMDAR in the SGC and dlPFC, the current study used immunoelectron microscopy (immunoEM) to quantitatively compare the synaptic and extrasynaptic expression patterns of NMDAR-GluN2B across excitatory and inhibitory neuron dendrites in rhesus macaque layer III SGC and dlPFC. We found a larger population of extrasynaptic NMDAR-GluN2B in dendrites of putative pyramidal neurons in SGC as compared to the dlPFC, while the dlPFC had a higher proportion of synaptic NMDAR-GluN2B. In contrast, in putative inhibitory dendrites from both areas, extrasynaptic expression of NMDAR-GluN2B was far more frequently observed over synaptic expression. These findings may provide insight into varying cortical vulnerability to alterations in excitability and neurodegenerative forces.
and : mythonyms that prevail in , , and .
Duque-Colorado J, García-Orozco L, Castillo-Martínez A … +1 more , Del Sol M
Front Neuroanat · 2025 · PMID 40248154 · Full text
Julius Caesar Arantius first described the hippocampus and proposed the term . Years later, French anatomists called the structure ram's horns, and a decade later, it was named cornu ammonis. Although both concepts were...
Julius Caesar Arantius first described the hippocampus and proposed the term . Years later, French anatomists called the structure ram's horns, and a decade later, it was named cornu ammonis. Although both concepts were first associated with the same structure, their use has expanded to include different but related structures. This situation can make understanding and applying the terminology more difficult. The objective of this work was to determine the presence of the terms , and their variants in , , and , evaluating their congruence in said terminologies, in addition to examining the etymology of both terms. We searched , , and for terms containing the concepts , , and their derivatives. We analyzed the terms and from their etymology by examining several Latin texts. This analysis included the dissection of the hippocampus and fornix and a review of the RAT rules. The etymological analysis indicated that the refers to a sea horse; however, the term also has a mythological background. , on the other hand, refers to the horns of an Egyptian god. The terminologies present discrepancies regarding the terms derived from and . Although both terms appear in various terminologies, they are mythonyms that fail to describe the structure they refer to or meet the requirements set by FIPAT.
Fenestrations of cerebral arteries and their correlation with brain aneurysms.
Ćetković M, Boljanović J, Bexheti E … +7 more , Vitošević F, Bogićević D, Milašinović S, Bexheti S, Ćetković D, Dožić A, Milisavljević M
Front Neuroanat · 2025 · PMID 40206441 · Full text
Fenestration of the intracranial artery is an anatomical remnant from the embryonic development of the vascular system. A cerebral aneurysm is a focal pathological dilation of the arterial wall. The occurrence of an aneu...
Fenestration of the intracranial artery is an anatomical remnant from the embryonic development of the vascular system. A cerebral aneurysm is a focal pathological dilation of the arterial wall. The occurrence of an aneurysm at the site of fenestration is rare in cerebral circulation but may have potential clinical implications. This study aimed to identify the frequencies of fenestrations and aneurysms, their locations, and their relationships. The vasculature of 35 adult brains was used for micromorphological dissection and analysis under a stereoscopic microscope, following an arterial injection with a mixture of formaldehyde, melted gelatin, and the solution of India ink. Additionally, we analyzed another group of vascular casts obtained from 15 brains injected with methyl methacrylate (MMA). A fenestration of the M1 segment of the middle cerebral artery (MCA) was sectioned for histological analysis. We also examined computed tomography (CT) angiograms of 1,230 patients, analyzed the data, and compared the findings with anatomical observations. In our group of 50 anatomical specimens, fenestrations were found in 12 brains (24%), affecting different cerebral arteries, with three cases showing double fenestrations on the same vessel. Aneurysms were observed in six brains (12%), always one per brain, with one case (2.00%) involving an aneurysm associated with the wall of a fenestration. Analysis of CT angiograms from 1,230 patients showed 26 arterial fenestrations (2.11%) in 26 patients, 28 aneurysms (2.28%), and one case (0.08%) where an aneurysm arose from a fenestration. The presence of an aneurysm on a fenestrated cerebral artery is a rare phenomenon, occurring far less frequently than isolated fenestrations or aneurysm formation.
Morphological analysis of the filum terminale and detailed description of the distal filum terminale externum: a cadaveric study.
Buloz-Osorio E, Ortega-Sánchez M, Royo-Salvador MB … +1 more , Rodríguez-Baeza A
Front Neuroanat · 2025 · PMID 40201577 · Full text
This observational, descriptive anatomical cadaveric study aimed to identify, characterize, and analyze the morphometric parameters of the filum terminale (FT) and macroscopically describe the distal insertion of the FTE...
This observational, descriptive anatomical cadaveric study aimed to identify, characterize, and analyze the morphometric parameters of the filum terminale (FT) and macroscopically describe the distal insertion of the FTE. The FT is a complex, three-dimensional, fibro-cellular structure of connective tissue and glial cells, extending from the conus medullaris (CM) to the dural sac (DS) and coccyx. It is divided into two segments: an intradural filum terminale internum (FTI) and extradural filum terminale externum (FTE). Few studies have comprehensively addressed its morphometric characteristics in the last decades. Thirty-eight embalmed (M = 16, F = 22) human cadavers were examined to determine the CM-FTI and DS-FTE vertebral levels and FT, FTI, and FTE lengths and widths. FTI and FTE segmental diameters, correlations, gross characteristics, tension, and mobility and were assessed. FTE distal insertion is thoroughly described. FT, FTI, and FTE mean lengths were 254.32 mm (±26.46), 152.75 mm (±22.02), and 106.64 mm (±12.21), respectively. The CM-FTI junction was observed at the L1-L2 disk space (32.1%), DS-FTE fusion in the upper third of S2 (39.3%), and FTI-DS fusion in the DS midline (46.4%). FT length and FTI, FTE lengths were directly correlated, as were all FTI diameters. FT gross characteristics were an irregular surface (71.4%), bright hue (57.1%), macroscopic FTI-CM contrast (64.3%), filiform shape (60.7%), and movement-resistance (53.6%). The FTE exhibited a flattened shape (64.3%), immobility (60.7%), distal insertion at Cx1 (67.8%) and one distal strand (60.7%). FTI segments ≥ 2 mm were uncommon (21.4%). The FTE distal insertion is variable, inserting as strands, with vascular tissue surrounding it. A distal coccygeal venous plexus and single or multiple strand-like insertions of the distal FTE are for the first time described in detail. Discrepancies in the morphometric parameters of the FT between studies highlight the need for standardized protocols, especially given the FT's anatomic-clinical importance and potential role as a neural progenitor niche. We provide a comprehensive basis for future standardized morphometric analyses, acknowledging the limitations of embalmed cadaveric studies.
Age-related alterations in functional and structural networks in the brain in macaque monkeys.
Ouchi K, Yamamoto S, Obara M … +2 more , Sugase-Miyamoto Y, Tsurugizawa T
Front Neuroanat · 2025 · PMID 40201576 · Full text
Resting-state networks (RSNs) have been used as biomarkers of brain diseases and cognitive performance. However, age-related changes in the RSNs of macaques, a representative animal model, are still not fully understood....
Resting-state networks (RSNs) have been used as biomarkers of brain diseases and cognitive performance. However, age-related changes in the RSNs of macaques, a representative animal model, are still not fully understood. In this study, we measured the RSNs in macaques aged 3-20 years and investigated the age-related changes from both functional and structural perspectives. The proportion of structural connectivity in the RSNs relative to the total fibers in the whole brain significantly decreased in aged macaques, whereas functional connectivity showed an increasing trend with age. Additionally, the amplitude of low-frequency fluctuations tended to increase with age, indicating that resting-state neural activity may be more active in the RSNs may increase with age. These results indicate that structural and functional alterations in typical RSNs are age-dependent and can be a marker of aging in the macaque's brain.
Development of catecholaminergic neurons of Otp-lineage in the medial extended amygdala and related forebrain centers.
Morales L, Desfilis E, Medina L
Front Neuroanat · 2025 · PMID 40177299 · Full text
Catecholaminergic (CA) neurons of the medial extended amygdala, preoptic region and adjacent alar hypothalamus have been involved in different aspects of social behavior, as well as in modulation of homeostasis in respon...
Catecholaminergic (CA) neurons of the medial extended amygdala, preoptic region and adjacent alar hypothalamus have been involved in different aspects of social behavior, as well as in modulation of homeostasis in response to different stressors. Previous data suggested that at least some CA neurons of the medial extended amygdala could originate in a hypothalamic embryonic domain that expresses the transcription factor Otp. To investigate this, we used Otp-eGFP mice (with permanent labeling of GFP in Otp cells) to analyze coexpression of GFP and tyrosine hydroxylase (TH) throughout ontogenesis by way of double immunofluorescence. Our results provide evidence that some forebrain CA cells belong to the Otp lineage. In particular, we found small subpopulations of TH cells that coexpress GFP within the medial extended amygdala, the periventricular preoptic area, the paraventricular hypothalamus, the periventricular hypothalamus, as well as some subdivisions of the basal hypothalamus. In some of the Otp cells, such as those of extended amygdala, the expression of TH appears to be transitory, in agreement with previous studies. The results open interesting questions about the role of these Otp versus non-Otp catecholaminergic subpopulations during development, network integration and in modulation of different functions, including homeostasis and social behaviors.
Imaging the enteric nervous system.
Hazart D, Moulzir M, Delhomme B … +2 more , Oheim M, Ricard C
Front Neuroanat · 2025 · PMID 40145027 · Full text
The enteric nervous system (ENS) has garnered increasing scientific interest due to its pivotal role in digestive processes and its involvement in various gastrointestinal and central nervous system (CNS) disorders, incl...
The enteric nervous system (ENS) has garnered increasing scientific interest due to its pivotal role in digestive processes and its involvement in various gastrointestinal and central nervous system (CNS) disorders, including Crohn's disease, Parkinson's disease, and autism. Despite its significance, the ENS remains relatively underexplored by neurobiologists, primarily because its structure and function are less understood compared to the CNS. This review examines both pioneering methodologies that initially revealed the intricate layered structure of the ENS and recent advancements in studying its three-dimensional (3-D) organization, both in fixed samples and at a functional level, or . Traditionally, imaging the ENS relied on histological techniques involving sequential tissue sectioning, staining, and microscopic imaging of single sections. However, this method has limitations representing the full complexity of the ENS's 3-D meshwork, which led to the development of more intact preparations, such as whole-mount preparation, as well as the use of volume imaging techniques. Advancements in 3-D imaging, particularly methods like spinning-disk confocal, 2-photon, and light-sheet microscopies, combined with tissue-clearing techniques, have revolutionized our understanding of the ENS's fine structure. These approaches offer detailed views of its cellular architecture, including interactions among various cell types, blood vessels, and lymphatic vessels. They have also enhanced our comprehension of ENS-related pathologies, such as inflammatory bowel disease, Hirschsprung's disease (HSCR), and the ENS's involvement in neurodegenerative disorders like Parkinson's (PD) and Alzheimer's diseases (AD). More recently, 2-photon or confocal imaging, combined with transgenic approaches for calcium imaging, or confocal laser endomicroscopy, have opened new avenues for functional studies of the ENS. These methods enable real-time observation of enteric neuronal and glial activity and their interactions. While routinely used in CNS studies, their application to understanding local circuits and signals in the ENS is relatively recent and presents unique challenges, such as accommodating peristaltic movements. Advancements in 3-D functional imaging are expected to significantly deepen our understanding of the ENS and its roles in gastrointestinal and neurological diseases, potentially leading to improved diagnostic and therapeutic strategies.
Del Río Hortega's insights into oligodendrocytes: recent advances in subtype characterization and functional roles in axonal support and disease.
López-Muguruza E, Peiró-Moreno C, Pérez-Cerdá F … +2 more , Matute C, Ruiz A
Front Neuroanat · 2025 · PMID 40145026 · Full text
Pío Del Río Hortega (1882-1945) was a giant of modern neuroscience and perhaps the most impactful member of Cajal's School. His contributions to clarifying the structure of the nervous system were key to understanding th...
Pío Del Río Hortega (1882-1945) was a giant of modern neuroscience and perhaps the most impactful member of Cajal's School. His contributions to clarifying the structure of the nervous system were key to understanding the brain beyond neurons. He uncovered microglia and oligodendrocytes, the latter until then named mesoglia. Most importantly, the characterization of oligodendroglia subtypes he made has stood the omics revolution that added molecular details relevant to comprehend their biological properties. Astounding as it may seem on today's eyes, he postulated a century ago that oligodendrocytes provide trophic support to axons, an idea that is now beyond doubt and under scrutiny as dysfunction at the axon-myelin unit is key to neurodegeneration. Here, we revised recent key advancements in oligodendrocyte biology that shed light on Hortega's ideas a century ago.
Antibiotics-induced dysbiosis impacts dendritic morphology of adult mouse cortical interneurons.
Nakhal MM, Mydeen AB, Yassin LK … +13 more , Almazrouei R, Alkamali R, Alsulaimi M, Elsaleh RI, BaniYas S, Al Houqani S, Al-Marzooq F, Hassane M, Voitetskii R, Statsenko Y, Allam M, Akour A, Hamad MIK
Front Neuroanat · 2025 · PMID 40124111 · Full text
INTRODUCTION: A growing body of evidence suggests that the gut microbiome may contribute to changes in brain morphology. The microbiota-gut-brain axis (MGBA) has been shown to influence neurogenesis, axon myelination, an...
INTRODUCTION: A growing body of evidence suggests that the gut microbiome may contribute to changes in brain morphology. The microbiota-gut-brain axis (MGBA) has been shown to influence neurogenesis, axon myelination, and synapse structure. However, it remains unclear whether the MGBA can influence the morphology and density of inhibitory GABAergic interneurons. The aim of this study was to determine whether antibiotic-induced dysbiosis (AID) is associated with alterations in dendritic morphology of GABAergic inhibitory interneurons in the medial entorhinal cortex (mEC), somatosensory cortex (SSC), motor cortex (MC), and hippocampus (Hp). METHODS: A cohort of six-month-old GAD-67-EGFP transgenic mice was treated with an antibiotic cocktail for two weeks, resulting in gut dysbiosis as validated by collecting stool samples at baseline and after treatment, then using next-generation sequencing of 16S ribosomal RNA. RESULTS: The results demonstrate that the proposed model effectively exhibited the defining features of gut dysbiosis, including a significant reduction in microbiome diversity, expansion of pathobionts, and loss of beneficial microbes. The AID group showed alterations in density and morphology of GABAergic interneurons in different brain areas. The mean dendritic length and mean dendritic segments of the SSC and Hp were found to be significantly decreased, while no such decrease was observed in the mEC or MC. Furthermore, the density of interneurons was decreased in the mEC, Hp, and SSC areas, while no change was observed in the MC area. DISCUSSION: The interneuron dysfunction plays a role in the pathogenesis of neurological disease. The findings of this study suggest that AID potentially influences the density and morphology of the interneurons, which may contribute to the development of neurological disorders.
Regional analysis of myelin basic protein across postnatal brain development of C57BL/6J mice.
Ozarkar SS, Patel RKR, Vulli T … +3 more , Friar CA, Burette AC, Philpot BD
Front Neuroanat · 2025 · PMID 40114847 · Full text
Healthy brain development hinges on proper myelination, with disruption contributing to a wide array of neurological disorders. Immunohistochemical analysis of myelin basic protein (MBP) is a fundamental technique for in...
Healthy brain development hinges on proper myelination, with disruption contributing to a wide array of neurological disorders. Immunohistochemical analysis of myelin basic protein (MBP) is a fundamental technique for investigating myelination and related disorders. However, despite decades of MBP research, detailed accounts of normal MBP progression in the developing mouse brain have been lacking. This study aims to address this gap by providing a detailed spatiotemporal account of MBP distribution across 13 developmental ages from postnatal day 2 to 60. We used an optimized immunohistochemistry protocol to overcome the challenges of myelin's unique lipid-rich composition, enabling more consistent staining across diverse brain structures and developmental stages, offering a robust baseline for typical myelination patterns, and enabling comparisons with pathological models. To support and potentially accelerate research into myelination disorders, we have made >1,400 high-resolution micrographs accessible online under the Creative Commons license.
Ayahuasca partially preserves striatal integrity in juvenile non-human primates exposed to chronic stress: evidence from stereological evaluation.
Lira-Bandeira WG, Mendonça Batista LAC, Medeiros-Bandeira AS … +9 more , Góis Morais PLA, Pereira LRF, Meiroz-Grilo MLP, Cavalcante JS, Santana MAD, Lima RRM, Galvão-Coelho NL, Ladd FVL, Nascimento ES
Front Neuroanat · 2025 · PMID 40060188 · Full text
INTRODUCTION: The striatum (St) integrates cognitive, motor, and limbic functions and plays a critical role in processing emotions, motivation, and rewards. It may undergo several morphophysiological changes in neuropsyc...
INTRODUCTION: The striatum (St) integrates cognitive, motor, and limbic functions and plays a critical role in processing emotions, motivation, and rewards. It may undergo several morphophysiological changes in neuropsychiatric diseases. Depression, a complex psychiatric disorder, affects millions of people around the world and leads to an increased risk of suicide, decreased quality of life, and functional impairment. Conventional treatments require prolonged use, leading to drug resistance; thus, new treatments and therapeutic strategies have been widely studied. Ayahuasca results from the joint infusion of the vine and Psychotria viridis leaves have psychoactive properties, and its use in depression has shown promising results. Our objective was to morphoquantitatively evaluate the effects of ayahuasca on the St in an already validated model of juvenile depression induced in a non-human primate. METHODS: Six marmosets were divided into three groups of two animals each. One group was kept in family life (FG), and two groups were socially isolated (IG). Isolation was carried out by separating the animal from all others in the colony. One of the isolated groups received doses of ayahuasca tea (AG) 3 days before and two times during the isolation period, while the other groups received the same dose of placebo. After 13 weeks of experimentation, euthanasia, and transcardiac perfusion were performed. The brains were sectioned and stained with thionin using the Nissl method. We employed stereological techniques to assess the striatum and investigate potential alterations in neuronal volume in socially isolated animals treated with ayahuasca. Equidistant sections of the caudate and putamen were analyzed for all measurements and selected by systematic and uniform sampling. RESULTS AND DISCUSSION: Striatal neurons in the IG group exhibited significantly smaller volumes compared to those in the FG and AG groups. Our findings suggest that ayahuasca may prevent extensive neuronal volume loss, as observed in the IG, by acting as a prophylactic agent and buffering neural structural changes during chronical social isolation.
The effects of amyloidosis and aging on glutamatergic and GABAergic synapses, and interneurons in the barrel cortex and non-neocortical brain regions.
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Front Neuroanat · 2025 · PMID 40012738 · Full text
Previous studies on changes in the distribution of GABAergic interneurons and excitation/inhibition (E/I) balance in Alzheimer's disease (AD) and aging were mainly conducted in the neocortex and hippocampus. However, the...
Previous studies on changes in the distribution of GABAergic interneurons and excitation/inhibition (E/I) balance in Alzheimer's disease (AD) and aging were mainly conducted in the neocortex and hippocampus. However, the limbic system is the primary and crucial location for AD progression. Therefore, in this study, we utilized AD and aging mouse models to investigate the E/I balance and the distribution of parvalbumin (PV)- and somatostatin (SST)-expressing cells in S1BF (barrel field of primary somatosensory cortex, barrel cortex), CA1 hippocampal area and brain regions beyond the neocortex and hippocampus, including retrosplenial cortex (RSC, which is composed of RSG and RSA), piriform cortex (Pir), amygdala (BMA), and hypothalamus (DM). We discovered that amyloidosis may disrupt the alignment of excitatory pre- and postsynaptic quantities. Amyloidosis reduces the quantity of synapses and SST cells, but does not impact the counts of PV cells. By contrast, aging is linked to a decline in synapses, I/E ratios, SST and PV cells. Amyloidosis affects the S1BF and BMA, while aging may harm all studied regions, including the S1BF, RSC, hippocampus, Pir, BMA, and DM. Aging mostly affects synapses and I/E ratios in Pir, BMA, and DM, and PV and SST interneurons in the hippocampus.
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