Spatial atlas of the mouse central nervous system at molecular resolution.

Spatially charting molecular cell types at single-cell resolution across the 3D volume is critical for illustrating the molecular basis of brain anatomy and functions. Single-cell RNA sequencing has profiled molecular cell types in the mouse brain1,2, but cannot capture their spatial organization. Here we used an in situ sequencing method, STARmap PLUS3,4, to profile 1,022 genes in 3D at a voxel size of 194 × 194 × 345 nm3, mapping 1.09 million high-quality cells across the adult mouse brain and spinal cord. We developed computational pipelines to segment, cluster and annotate 230 molecular cell types by single-cell gene expression and 106 molecular tissue regions by spatial niche gene expression. Joint analysis of molecular cell types and molecular tissue regions enabled a systematic molecular spatial cell-type nomenclature and identification of tissue architectures that were undefined in established brain anatomy. To create a transcriptome-wide spatial atlas, we integrated STARmap PLUS measurements with a published single-cell RNA-sequencing atlas1, imputing single-cell expression profiles of 11,844 genes. Finally, we delineated viral tropisms of a brain-wide transgene delivery tool, AAV-PHP.eB5,6. Together, this annotated dataset provides a single-cell resource that integrates the molecular spatial atlas, brain anatomy and the accessibility to genetic manipulation of the mammalian central nervous system.

Wake-like skin patterning and neural activity during octopus sleep.

While sleeping, many vertebrate groups alternate between at least two sleep stages: rapid eye movement and slow wave sleep1-4, in part characterized by wake-like and synchronous brain activity, respectively. Here we delineate neural and behavioural correlates of two stages of sleep in octopuses, marine invertebrates that evolutionarily diverged from vertebrates roughly 550 million years ago (ref. 5) and have independently evolved large brains and behavioural sophistication. 'Quiet' sleep in octopuses is rhythmically interrupted by approximately 60-s bouts of pronounced body movements and rapid changes in skin patterning and texture6. We show that these bouts are homeostatically regulated, rapidly reversible and come with increased arousal threshold, representing a distinct 'active' sleep stage. Computational analysis of active sleep skin patterning reveals diverse dynamics through a set of patterns conserved across octopuses and strongly resembling those seen while awake. High-density electrophysiological recordings from the central brain reveal that the local field potential (LFP) activity during active sleep resembles that of waking. LFP activity differs across brain regions, with the strongest activity during active sleep seen in the superior frontal and vertical lobes, anatomically connected regions associated with learning and memory function7-10. During quiet sleep, these regions are relatively silent but generate LFP oscillations resembling mammalian sleep spindles11,12 in frequency and duration. The range of similarities with vertebrates indicates that aspects of two-stage sleep in octopuses may represent convergent features of complex cognition.

New virtual platform for teaching comparative animal neuroanatomy based on metameric slices of the central nervous system.

With the limitations imposed by the COVID-19 pandemic, new technologies were used as methods to continue teaching and learning activities. This scenario brought forth the need to develop online tools for teaching. Therefore, this research aimed to develop a digital platform linking the knowledge about the central nervous system (CNS) anatomy from feline, equine, and sheep models. The platform was produced from the analysis of a collection of mesoscopic slides made from the sequenced cross-section of the CNS of a feline, an equine, and a sheep. All sections were analysed and stained using the Paul-Wiegert modified technique. The platform was organized in four modules: (1) Neuroanatomy of the Central Nervous System; (2) Neuroanatomy of Feline; (3) Neuroanatomy of Equine; and (4) Neuroanatomy of sheep. For each module, an explanatory document in PDF was developed, as well as video lectures and a descriptive atlas identifying the structures present in the encephalon and in the cervical part of the spinal cord. Even though there are numerous online platforms that allow the study of veterinary anatomy of different species and organs, the veterinary neuroanatomy platform presented here is the first platform that conjointly addresses the CNS anatomy of felines, equines, and sheep. Future research applying this platform as an aid to the study of neuroanatomy by students, teachers, and veterinary professionals should validate its use as a complementary tool for teaching and learning animal neuroanatomy.

Development of an interactive multidisciplinary platform for the bovine neuroanatomy study / Desarrollo de una plataforma interactiva multidisciplinar para el estudio de la neuroanatomía bovina

SUMMARY: The anatomy study is part of the basic cycle of disciplines that composes Veterinary Medicine college curriculum, and its comprehension is essential for other courses subject understanding. However, the current student's profile, the reduced time frame of superior education programs, and the multidisciplinary approach nowadays have made anatomy teaching method outdated and ineffective. Addressing the problem we developed an interactive and multidisciplinary platform based on the blended learning methodology, which could serve as a valuable tool for bovine neuroanatomy comprehension. To produce a new study tool, photos from bovine specimens fixed in formaldehyde, platinated brain pieces sectioned in a metameric order, as well as histological slides of the bovine central nervous system were used. These materials were applied to photos and schemes production, that were correlated with image exams correlation, as well as written content and videotaped classes. The obtained content was compiled into a digital platform, that can serve as an effective additional method to bovine central nervous system study. Furthermore, our results serve as a guide for the development of other blended learning methodologies in veterinary medicine and anatomy teaching. The platform provides a great tool for those who wish to accomplish a better understanding of bovine neuroanatomy and its clinical, surgical and image diagnosis correlations.

El estudio de la anatomía forma parte del ciclo básico de disciplinas que componen el currículo de la facultad de Medicina Veterinaria, y su comprensión es fundamental para el entendimiento de las materias de otros cursos. Sin embargo, el perfil del estudiante actual, la reducción de los tiempos de los programas de educación superior y el enfoque multidisciplinario actual han hecho que el método de enseñanza de la anatomía sea obsoleto e ineficaz. Abordando el problema desarrollamos una plataforma interactiva y multidisciplinar basada en la metodología blended learning, que podría servir como una valiosa herramienta para la comprensión de la neuroanatomía bovina. Para producir una nueva herramienta de estudio, se utilizaron fotografías de especímenes bovinos fijados en formaldehído, piezas de cerebro plastinadas y seccionadas en un orden metamérico, así como láminas histológicas del sistema nervioso central bovino. Estos materiales se utilizaron en la producción de fotos y esquemas, que se correlacionaron con exámenes de imágenes, así como contenido escrito y clases grabadas en video. El contenido obtenido se compiló en una plataforma digital, que puede servir como un método adicional y eficaz para el estudio del sistema nervioso central bovino. Además, nuestros resultados sirven como guía para el desarrollo de otras metodologías de aprendizaje semipresencial en la enseñanza de la medicina veterinaria y la anatomía. La plataforma proporciona una gran herramienta para aquellos que deseen lograr una mejor comprensión de la neuroanatomía bovina y sus correlaciones clínicas, quirúrgicas y de diagnóstico por imágenes.

Comparative topographical description of the central nervous system of the macaw (Ara ararauna) and the owl (Tyto furcata)Comparative Topographical Description of the Central Nervous System of the Macaw (Ara ararauna) and the Owl (Tyto furcata) / Descripción topográfica comparativa del sistema nervioso central del guacamayo (Ara ararauna) y el búho (Tyto furcata)

SUMMARY: The study of animal neurology has historically focused on the closest descendants of humans, such as monkeys and chimpanzees. Because of this, the neurology of birds remains poorly studied and understood by humans compared to other groups of animals. Thus, the objective was to describe the central nervous system to better understand its functioning, correlating the findings with the role it plays in the physiology and biology of birds, comparing species with different behaviors between herbivores and carnivores, filling gaps in the literature serving as subsidy for future research.

RESUMEN: El estudio de la neurología animal se ha centrado históricamente en los descendientes más cercanos de los humanos, como los monos y los chimpancés. Debido a esto, la neurología de las aves sigue siendo poco estudiada y comprendida, en comparación con la de otros grupos de animales. Así, el objetivo fue describir el sistema nervioso central para comprender mejor su funcionamiento, correlacionando los hallazgos con el rol que juega en la fisiología y biología de las aves, comparando especies con diferentes comportamientos entre herbívoros y carnívoros y llenando vacíos en la literatura que sirvan como base para futuras investigaciones.

Age-associated suppression of exploratory activity during sickness is linked to meningeal lymphatic dysfunction and microglia activation.

Peripheral inflammation triggers a transient, well-defined set of behavioral changes known as sickness behavior1-3, but the mechanisms by which inflammatory signals originating in the periphery alter activity in the brain remain obscure. Emerging evidence has established meningeal lymphatic vasculature as an important interface between the central nervous system (CNS) and the immune system, responsible for facilitating brain solute clearance and perfusion by cerebrospinal fluid (CSF)4,5. Here, we demonstrate that meningeal lymphatics both assist microglial activation and support the behavioral response to peripheral inflammation. Ablation of meningeal lymphatics results in a heightened behavioral response to IL-1ß-induced inflammation and a dampened transcriptional and morphological microglial phenotype. Moreover, our findings support a role for microglia in tempering the severity of sickness behavior with specific relevance to aging-related meningeal lymphatic dysfunction. Transcriptional profiling of brain myeloid cells shed light on the impact of meningeal lymphatic dysfunction on microglial activation. Furthermore, we demonstrate that experimental enhancement of meningeal lymphatic function in aged mice is sufficient to reduce the severity of exploratory abnormalities but not pleasurable consummatory behavior. Finally, we identify dysregulated genes and biological pathways, common to both experimental meningeal lymphatic ablation and aging, in microglia responding to peripheral inflammation that may result from age-related meningeal lymphatic dysfunction.

WAPM-World Association of Perinatal Medicine Practice Guidelines: Fetal central nervous system examination.

These practice guidelines follow the mission of the World Association of Perinatal Medicine in collaboration with the Perinatal Medicine Foundation, bringing together groups and individuals throughout the world, with the goal of improving the ultrasound assessment of the fetal Central Nervous System (CNS) anatomy. In fact, this document provides further guidance for healthcare practitioners for the evaluation of the fetal CNS during the mid-trimester ultrasound scan with the aim to increase the ability in evaluating normal fetal anatomy. Therefore, it is not intended to establish a legal standard of care. This document is based on consensus among perinatal experts throughout the world, and serves as a guideline for use in clinical practice.

New advances in immune components mediating viral control in the CNS.

Protective immune responses in the central nervous system (CNS) must act efficiently but need to be tightly controlled to avoid excessive damage to this vital organ. Under homeostatic conditions, the immune surveillance of the CNS is mediated by innate immune cells together with subsets of memory lymphocytes accumulating over lifetime. Accordingly, a wide range of immune responses can be triggered upon pathogen infection that can be associated with devastating clinical outcomes, and which most frequently are due to neurotropic viruses. Here, we discuss recent advances about our understanding of anti-viral immune responses with special emphasis on mechanisms operating in the various anatomical compartments of the CNS.

Cephalochordates: A window into vertebrate origins.

How vertebrates evolved from their invertebrate ancestors has long been a central topic of discussion in biology. Evolutionary developmental biology (evodevo) has provided a new tool-using gene expression patterns as phenotypic characters to infer homologies between body parts in distantly related organisms-to address this question. Combined with micro-anatomy and genomics, evodevo has provided convincing evidence that vertebrates evolved from an ancestral invertebrate chordate, in many respects resembling a modern amphioxus. The present review focuses on the role of evodevo in addressing two major questions of chordate evolution: (1) how the vertebrate brain evolved from the much simpler central nervous system (CNS) in of this ancestral chordate and (2) whether or not the head mesoderm of this ancestor was segmented.

The central nervous system of whip spiders (Amblypygi): Large mushroom bodies receive olfactory and visual input.

Whip spiders (Amblypygi) are known for their nocturnal navigational abilities, which rely on chemosensory and tactile cues and, to a lesser degree, on vision. Unlike true spiders, the first pair of legs in whip spiders is modified into extraordinarily long sensory organs (antenniform legs) covered with thousands of mechanosensory, olfactory, and gustatory sensilla. Olfactory neurons send their axons through the leg nerve into the corresponding neuromere of the central nervous system, where they terminate on a particularly large number (about 460) of primary olfactory glomeruli, suggesting an advanced sense of smell. From the primary glomeruli, olfactory projection neurons ascend to the brain and terminate in the mushroom body calyx on a set of secondary olfactory glomeruli, a feature that is not known from olfactory pathways of other animals. Another part of the calyx receives visual input from the secondary visual neuropil (the medulla). This calyx region is composed of much smaller glomeruli ("microglomeruli"). The bimodal input and the exceptional size of their mushroom bodies may support the navigational capabilities of whip spiders. In addition to input to the mushroom body, we describe other general anatomical features of the whip spiders' central nervous system.

Preservation of neurons in an AD 79 vitrified human brain.

Detecting the ultrastructure of brain tissue in human archaeological remains is a rare event that can offer unique insights into the structure of the ancient central nervous system (CNS). Yet ancient brains reported in the literature show only poor preservation of neuronal structures. Using scanning electron microscopy (SEM) and advanced image processing tools, we describe the direct visualization of neuronal tissue in vitrified brain and spinal cord remains which we discovered in a male victim of the AD 79 eruption in Herculaneum. We show exceptionally well preserved ancient neurons from different regions of the human CNS at unprecedented resolution. This tissue typically consists of organic matter, as detected using energy-dispersive X-ray spectroscopy. By means of a self-developed neural image processing network, we also show specific details of the neuronal nanomorphology, like the typical myelin periodicity evidenced in the brain axons. The perfect state of preservation of these structures is due to the unique process of vitrification which occurred at Herculaneum. The discovery of proteins whose genes are expressed in the different region of the human adult brain further agree with the neuronal origin of the unusual archaeological find. The conversion of human tissue into glass is the result of sudden exposure to scorching volcanic ash and the concomitant rapid drop in temperature. The eruptive-induced process of natural vitrification, locking the cellular structure of the CNS, allowed us to study possibly the best known example in archaeology of extraordinarily well-preserved human neuronal tissue from the brain and spinal cord.

The internal cranial anatomy of Champsosaurus (Choristodera: Champsosauridae): Implications for neurosensory function.

Although isolated Champsosaurus remains are common in Upper Cretaceous sediments of North America, the braincase of these animals is enigmatic due to the fragility of their skulls. Here, two well-preserved specimens of Champsosaurus (CMN 8920 and CMN 8919) are CT scanned to describe their neurosensory structures and infer sensory capability. The anterior portion of the braincase was poorly ossified and thus does not permit visualization of a complete endocast; however, impressions of the olfactory stalks indicate that they were elongate and likely facilitated good olfaction. The posterior portion of the braincase is ossified and morphologically similar to that of other extinct diapsids. The absence of an otic notch and an expansion of the pars inferior of the inner ear suggests Champsosaurus was limited to detecting low frequency sounds. Comparison of the shapes of semicircular canals with lepidosaurs and archosauromorphs demonstrates that the semicircular canals of Champsosaurus are most similar to those of aquatic reptiles, suggesting that Champsosaurus was well adapted for sensing movement in an aquatic environment. This analysis also demonstrates that birds, non-avian archosauromorphs, and lepidosaurs possess significantly different canal morphologies, and represents the first morphometric analysis of semicircular canals across Diapsida.

Curricular changes: the impact on medical students knowledge of neuroanatomy.

BACKGROUND: Although neuroanatomy is considered an essential requirement in medical curriculum, its teaching has undergone many changes in recent years, with most medical schools starting to implement an integrated approach. The current paper describes the comparative evaluation of the neuroanatomy knowledge scores of medical students who attended two different pedagogic approaches of neuroanatomy in the Faculty of Medicine of the University of Porto. METHODS: Forty fourth-year medical students who attended a traditional stand-alone approach and 42 third-year medical students who attended an integrated approach completed a written test of knowledge. RESULTS: Although there were some significant differences, the results globally revealed no statistically significant difference between the neuroanatomy knowledge scores of the integrated and traditional education groups, with most students obtaining a passing score in both curricula. CONCLUSIONS: Our study is the first attempt to compare the knowledge acquired by medical students from two different pedagogical approaches to neuroanatomy. Although the integrated curricula were only implemented in the Faculty of Medicine of the University of Porto a few years ago, the students who attended these curricula obtained similar scores as those obtained by the students of the traditional curriculum. This finding suggests that an integrated curriculum can be, in light of curricular reform, an efficient approach to teaching neuroanatomy to medical students.

Changes in neurocognitive function and central nervous system structure in childhood acute lymphoblastic leukaemia survivors after treatment: a meta-analysis.

Acute lymphoblastic leukaemia (ALL) is the most common malignancy in children. Although the survival rate has increased dramatically over the last decades, patients struggle with the adverse side effects of treatment. Treatment for ALL includes chemotherapy and irradiation - both of which are linked to cognitive impairments and alterations in central nervous system (CNS) structure and function detected by neuroimaging and in neurocognitive studies. The present article is a meta-analysis of the existing evidence for the mechanisms underlying changes in the CNS and neurocognitive function in ALL survivors after treatment. We found that compared with controls, ALL survivors develop: (i) cognitive sequelae in intelligence, academics, attention, memory, processing speed and executive function domains; (ii) decreased grey and white matter volume in cortical and several subcortical brain regions, with functional changes particularly in frontal regions and the hippocampus; (iii) neurocognitive impairments related to CNS changes; and (iv) reduction, but not resolution, of late neurocognitive sequelae in patients in whom prophylactic irradiation was replaced by systemic/intrathecal chemotherapy. Continued work with advanced functional magnetic resonance imaging techniques will hopefully allow the detection of early CNS changes as biomarkers to help guide early diagnosis and intervention for neurocognitive defects in patients with childhood ALL.

Unveiling the Insular Lobe of Reil: Neurophysiological and Anatomical Features

The insular lobe has long been investigated, from its anatomical descriptions to its neurophysiological activity. Located in a central location, the insular lobe participates in several afferent and efferent pathways, forming part of the eloquent and fundamental structures that make up the central core of the brain. The lobe of the insula has participation in language function, such as speech, sensory (e.g., taste), limbic, autonomic (visceral), also forming part of complex associative circuits, including part of the circuits of mirror neurons. Several functional descriptions attributed to the insular lobe have beenmade in patients suffering fromcerebrovascular diseases, as well as in those with epilepsy. Much progress and many descriptions have also been made in patients with tumors. Despite much information already available about the insular lobe, it is likely that much will be discovered in the coming years.

Comparing the Superficial Vasculature of the Central Nervous System in Six Laboratory Animals: A Hypothesis About the Role of the "Circle of Willis".

We provide images of the entire central nervous system vasculature, and compare the anatomical findings in six different laboratory animals. A detailed understanding of the specific anatomy for each is important in the design of experimental modeling and for understanding the specific function of each target organ. Six different types of animals, the Korean wild mouse, C57BL/6J mouse, F344 rat, mongolian gerbil, Syrian hamsters, and guinea pigs, were included. To stain the blood vessels in each of the animals, Alcian blue reagent was used to perfuse each species. The bifurcation and anastomotic patterns of the anterior cerebral arteries differed in each species. The vascular supply to the olfactory nerve was visualized as a single artery supplying both olfactory nerves, and arteries supplying the lateral portion of the olfactory nerves originating from the olfactory bulb area. The posterior communicating arteries of the six animals demonstrated unique morphologies. The shape of the hypophyseal portal system varied by species. Most animals used in this study had a hexagonal Circle of Willis, except for the Korean wild mouse. Using this approach, we successfully mapped the brain vascular system in six different species of animals. This information and the images created can guide other researchers as they design research studies and create experimental models for new surgical procedures and approaches. Anat Rec, 2019. © 2019 Wiley Periodicals, Inc. Anat Rec, 302:2049-2061, 2019. © 2019 American Association for Anatomy.

[Lymphatic system in central nervous system]. / Système lymphatique et cerveau.

The considerable metabolic activity of the central nervous system (CNS) requires an efficient system of tissue drainage and detoxification. The CNS is however devoid of lymphatic vessels, a vasculature ensuring interstitial fluid drainage and immune survey in other organs. A unique system of drainage has recently been identified between the cerebrospinal fluid (CSF), brain interstitial fluids and meningeal lymphatic vessels. This system is coupling a cerebral "glymphatic" flow with a meningeal lymphatic vasculature. The "glymphatic" system includes perivascular spaces and astrocytes, and drains interstitial fluids, from and towards the CSF. Meningeal lymphatic vessels are functionally linked to the cerebral "glymphatic" efflux by clearing intracerebral macromolecules and antigens towards the peripheral lymphatic system. The "glymphatic"-"meningeal lymphatics" system is potentially offering new therapeutic targets to improve cerebral drainage and immune survey in human CNS diseases.

A brief review of recent discoveries in human anatomy.

In the last few years, a cluster of anatomical discoveries has been reported which overturned the long existing dogmas about the structure and function of human body. First to come was the discovery that established the existence of a lymphatic system pertaining to the central nervous system (CNS). CNS was believed to be anatomically immune privileged owing to the absence of any lymphatics and presence of the blood-brain barrier around it, but latest research has established beyond any reasonable doubt that true lymphatic channels carry immune cells in meninges thus challenging the existing theory. Studies also supported the presence of a 'Glymphatic system' (created by the perivascular spaces lined with the leptomeninges and a sheath of glial cells) in the CNS draining interstitial metabolic waste from CNS. The second discovery unraveled the previously unknown parts of the human mesentery in adult and established that it is a continuous entity all along the intra-abdominal gut tube against the previous notion that it is fragmented in the adult humans. A very recently reported third discovery demonstrated a previously unknown tissue component-'interstitium'-a networked collagen bound fluid-filled space existent in a number of human organs. All these structures bear considerable applied importance towards the pathogenesis, prognostic and diagnostic investigations and management of human diseases. This article attempts to present a brief review of all three remarkable discoveries and emphasizes their applied importance within the realm of medical sciences.

Our current understanding of the lymphatics of the brain and spinal cord.

The lymphatic system, segregated from the blood vascular system, is an essential anatomical route along which interstitial fluid, solutes, lipids, immune cells, and cellular debris, are conveyed. However, the way these mechanisms operate within the cranial compartment is mostly unknown. Herein, we review current understanding of the meningeal lymphatics, described anatomically over a century ago yet still poorly understood from a functional standpoint. We will delineate the cellular mechanisms by which the meningeal lymphatics are formed and discuss their unique anatomy. Furthermore, this review will discuss the recently-coined "glymphatic system" and the manner by which cerebrospinal fluid (CSF) and interstitial fluid (ISF) are exchanged and thus drained by the meningeal lymphatic vasculature as a key route for conveying cellular waste, solutes, and immune traffic to the deep cervical lymph nodes. The clinical relevance of the meningeal lymphatics will also be described, as they are relevant to various common defects of the lymphatic system. Clin. Anat. 32:117-121, 2019. © 2018 Wiley Periodicals, Inc.