Frontiers in Neuroanatomy最新文献

Introduction: Mutations in the methyl-CpG-binding protein-2 gene (MECP2), which cause Rett syndrome (RTT), disrupt neuronal activity; however, the impact of the MECP2 loss-of-function on the cytoarchitecture of medial entorhinal cortex layer II (MECII) neurons-crucial for spatial memory and learning-remains poorly understood.

Methods: In this study, we utilized Golgi staining and neuron tracing in the Mecp2^+/- mouse model of RTT to investigate the pyramidal and stellate cell alterations in MECII.

Results and discussion: Our findings revealed that pyramidal cells displayed a significant reduction in apical dendritic length, soma size, and spine density, while basal dendrites showed increased dendritic complexity and branching. On the other hand, stellate cells exhibited dendritic hypertrophy along with increased soma size, primary dendrites, and localized increase in dendritic intersections, despite an overall reduction in total dendritic length and spine density. These findings underscore the notion that MECP2 loss-of-function can disrupt MECII pyramidal and stellate cell cytoarchitecture in a cell-type-specific manner, emphasizing its critical role in maintaining proper dendritic morphology in circuits, which is crucial for learning and memory.

Introduction: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms and heterogeneous cognitive impairments influenced by factors such as age, disease duration, and severity. Traditional neuropsychological assessments often fall short in capturing the multifaceted nature of PD-related cognitive dysfunction due to their reliance on single test metrics. This study provides empirical support for the implementation of domain-based cognitive assessments, structured in line with Movement Disorder Society recommendations, to provide a multidimensional evaluation of cognitive profiles in PD patients.

Methods: Neuropsychological and clinical data were analyzed from 316 PD patients recruited from three Spanish hospitals-Hospital Clínico San Carlos (Madrid), the University Complejo Universitario de Santiago de Compostela (Galicia), and Hospital Virgen del Rocío (Sevilla)- and a control group of 96 older individuals, whose age difference from the PD group was statistically significant. Five cognitive domains were constructed, addressing attention/working memory, executive functions, memory, visuospatial abilities, and language, using composite z-scores derived from standardized neuropsychological tests.

Results: Latent Cluster Analysis identified three distinct cognitive profiles: (1) a fronto-striatal profile characterized by mild deficits in executive and attention functions and intact visuospatial abilities, (2) a posterior cortical profile marked by severe memory and visuospatial impairments but strong language performance, and (3) a preserved profile displaying mild deficits across multiple domains. Comparisons between PD clusters and controls revealed significant differences in cognitive trajectories, emphasizing the value of a domain-based approach for differentiating neurodegenerative patterns from normal aging.

Discussion: The findings highlight the potential of domain-based assessments to unify data across diverse samples, fostering standardized cross-cohort comparisons and facilitating large-scale research initiatives. By enabling methodological consistency, this approach provides a robust framework for advancing the understanding of cognitive dysfunctions in PD and improving clinical decision-making.

For most non-diving mammals, lack of O₂ (hypoxia) has detrimental effects on brain function. Seals, however, display a series of systemic, cellular, and molecular adaptations that enable them to tolerate repeated episodes of severe hypoxia. One as yet unresolved question is whether seal neurons in part employ anaerobic metabolism during diving: the "reverse astrocyte-neuron lactate shuttle" (rANLS) hypothesis postulates that seal neurons, by shuttling lactate to the astrocytes, may be relieved (1) from the lactate burden and (2) from subsequent ROS-production as lactate is oxidized by astrocytes upon re-oxygenation after the dive. Here, we have investigated this possibility, through histological and functional comparisons of the metabolic characteristics of neocortical neurons and astrocytes from the deep-diving hooded seal (Cystophora cristata), using mice (Mus musculus) as a non-diving control. We found that seal astrocytes have higher mitochondrial density and larger mitochondria than seal neurons, and that seal neurons have an atypical and significantly higher representation of the monocarboxylate lactate exporter MCT4 compared to mouse neurons. Also, measurements of mitochondrial O₂ consumption suggest that the aerobic capacity of primary seal astrocytes is at least equal to that of primary seal neurons. Transcriptomics data from seals vs. mice suggest that specific adaptations to the electron transport system in seals may contribute to enhance hypoxia tolerance. These observations are consistent with the rANLS hypothesis.

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.

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.

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.

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.

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.