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 GFAP and strong GLUL (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.

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.

Autism spectrum disorder (ASD) and speech and language disorder (SLD) are distinct neurodevelopmental conditions, yet both share overlapping communication impairments. Forkhead box P2 (FOXP2), a key transcription factor involved in speech and language development, harbors pathogenic mutations such as R553H, which cause SLD and have been suggested to contribute to aspects of ASD-related phenotypes. This review synthesizes insights from animal models to explore the molecular mechanisms by which Foxp2 mutations disrupt the development of the cerebral cortex, thalamus, and enteric nervous system. We highlight findings from heterozygous Foxp2 mutants and discuss severe phenotypes observed in homozygous Foxp2 mutants (Foxp2R552H/R552H and Foxp2R552H/R552H/mCherry-Tg mice), including profound ultrasonic vocalization deficits, brain malformations, and early lethality. Notably, these mice exhibit gastrointestinal abnormalities involving the epithelium, smooth muscle, and enteric nervous system, which are linked to impaired autoregulation and interference with Wnt signaling during development. Such observations underscore the relevance of the brain-gut-microbiome axis and Hirschsprung-like pathology in neurodevelopmental disorders. Finally, this review discusses future directions using gene-editing approaches in non-mammalian models-zebra finches, zebrafish, and Drosophila-to dissect neural networks underlying intellectual disability and communication deficits. Collectively, these studies provide a framework for understanding FOXP2-related molecular mechanisms in the pathogenesis of ASD and SLD.

Accurate quantification of cellular composition is fundamental to understanding the structural and functional organization of the cerebral cortex. In the present study, we quantified the proportions of neurons, glia, and vascular cells (primarily endothelial cells) across the full cortical thickness (layers I-VI) of the mouse primary somatosensory cortex (S1HL) and the human temporal cortex (BA21) using immunocytochemical techniques and a direct 3D counting method. Over 25,000 cells in the mouse and 13,000 cells in the human cortex were individually identified and classified. For this purpose, we utilized EspINA software, which enables precise cell identification and volumetric analysis while preserving laminar and spatial context. Our results reveal marked species-specific differences in cellular proportions: neurons represent approximately 60% of all cells in the mouse S1HL but only 30% in the human BA21. These differences are reflected in the glia-to-neuron ratio (GNR) and non-neuron-to-neuron ratio (nNNR), which were consistently below 1.0 in the mouse (GNR: 0.4; nNNR: 0.6) but significantly higher in the human samples (GNR: 1.5; nNNR: 2.3). By overcoming the limitations of traditional stereological and tissue-homogenization techniques, this study provides a detailed laminar characterization of the cellular composition in these particular cortical regions (mouse S1HL and human BA21).

The corticospinal tract (CST) and reticulospinal tract (RST) represent the core descending pathways within the central nervous system for motor control. This review elucidates the anatomical and functional interplay. Anatomically, the CST and RST fibers are spatially proximate within the spinal cord and are integrated into a continuous regulatory axis via the corticoreticular pathway. Functionally, they exhibit both synergy and specialization: the CST primarily governs contralateral distal limb fine motor control, whereas the RST, operating in a bilateral mode, regulates axial and proximal body movements, postural stability, and adaptation to strength training. Notably, following CST damage (e.g., stroke or spinal cord injury), the RST demonstrates remarkable plasticity and serves as a critical substrate for functional compensation and recovery. Furthermore, an imbalance in CST-RST function has been implicated in the pathophysiology of conditions such as post-stroke spasticity and multiple sclerosis. Therapeutic strategies targeting the CST-RST network, including neuromodulation and molecular interventions aimed at promoting axonal regeneration and modulating network excitability, present promising new directions for the treatment of neurological disorders. Future research should focus on deciphering the specific interactions at the spinal interneuron level to advance the development of precise rehabilitation strategies.

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.

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 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. 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. 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. 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.

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 in situ and ex vivo 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.

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.