Frontiers in Neuroanatomy最新文献

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.

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.

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 (Callithrix jacchus). 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/mm³ 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.

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.

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.

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.

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 Xenopus laevis 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.

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 (p = 2.49e-04), smaller ventral GM horns (p < 0.005), deeper ventral commissures (p = 5.58e-13), and an increase in CC area (from 1925.58 ± 630.16 μm² to 2199.50 ± 569.44 μm²). Looking at sex-related differences, females showed higher variability across several parameters, with subtle differences in GM organization (p < 0.05) and CC morphology (mean area = 2146.39 ± 632.91 μm² in females vs. 1998.36 ± 589.85 μm² in males). Along the rostro-caudal axis, WM size, as well as GM dorsal and ventral horn dimensions, differed significantly across spinal segments (p < 0.005). CC position also shifted dorsally in cervical and lumbar regions depending on age and sex (p < 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 (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.