A historical perspective on training students to create standardized maps of novel brain structure: Newly-uncovered resonances between past and present research-based neuroanatomy curricula.

Recent efforts to reform postsecondary STEM education in the U.S. have resulted in the creation of course-based undergraduate research experiences (CUREs), which, among other outcomes, have successfully retained freshmen in their chosen STEM majors and provided them with a greater sense of identity as scientists by enabling them to experience how research is conducted in a laboratory setting. In 2014, we launched our own laboratory-based CURE, Brain Mapping & Connectomics (BMC). Now in its seventh year, BMC trains University of Texas at El Paso (UTEP) undergraduates to identify and label neuron populations in the rat brain, analyze their cytoarchitecture, and draw their detailed chemoarchitecture onto standardized rat brain atlas maps in stereotaxic space. Significantly, some BMC students produce atlas drawings derived from their coursework or from further independent study after the course that are being presented and/or published in the scientific literature. These maps should prove useful to neuroscientists seeking to experimentally target elusive neuron populations. Here, we review the procedures taught in BMC that have empowered students to learn about the scientific process. We contextualize our efforts with those similarly carried out over a century ago to reform U.S. medical education. Notably, we have uncovered historical records that highlight interesting resonances between our curriculum and that created at the Johns Hopkins University Medical School (JHUMS) in the 1890s. Although the two programs are over a century apart and were created for students of differing career levels, many aspects between them are strikingly similar, including the unique atlas-based brain mapping methods they encouraged students to learn. A notable example of these efforts was the brain atlas maps published by Florence Sabin, a JHUMS student who later became the first woman to be elected to the U.S. National Academy of Sciences. We conclude by discussing how the revitalization of century-old methods and their dissemination to the next generation of scientists in BMC not only provides student benefit and academic development, but also acts to preserve what are increasingly becoming "lost arts" critical for advancing neuroscience - brain histology, cytoarchitectonics, and atlas-based mapping of novel brain structure.

Optimizing techniques for injecting DiI into the brain nuclei of neonatal mice P6 - C57Bl6/CBA.

DiI (1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate) is a lipophilic dye used to research the intracerebral connections of neonatal animals. This dye is most frequently used in the form of dry crystals, but injections of the marker in this state into the mouse brain nuclei, such as MHb (2 cases), LHbM (2 cases), LPA (3 cases) and TS (1 case), clearly revealed excessive lateral diffusion marker into the tissue. Eventually, all the investigated cases except the LPA gave a false positive result. To find the optimal method of marker injection,DiI-kerosene liquid films (3 cases in the MHb); DiI-kerosene gelatinous paste (3 cases in the MHb); injections of insoluble DiI crystals from a solution of 99% dmso (3 cases in the MHb) and 70% ethanol (3 cases in the MHb, 2 cases in the LHbM, 4 cases in the TS) were tested. Injections of DiI in the form of undissolved crystals from a 70% ethanol solution gave a minimal level of side diffusion in all the studied cases. This method of injection is optimal and recommended for use.

A Method for Parasagittal Sectioning for Neuroanatomical Quantification of Brain Structures in the Adult Mouse.

In this article, we present a standardized protocol for fast and robust neuroanatomical phenotyping of the adult mouse brain, which complements a previously published article (doi: 10.1002/cpmo.12) in Current Protocols in Mouse Biology. It is aimed at providing an experimental pipeline within an academic research setting from experimental work to data analysis. Our analysis focuses on one single parasagittal plane, covering the majority of brain regions involved in higher order cognitions such as the cortex, hippocampus, and cerebellum, for a total of 166 parameters of area, length, and cell-level measurements in contrast to 78 parameters in our previously published coronal screen. Benefits of using parasagittal analysis for large-scale neuroanatomic screens are discussed. © 2018 by John Wiley & Sons, Inc.

Primate Brain Anatomy: New Volumetric MRI Measurements for Neuroanatomical Studies.

Since the publication of the primate brain volumetric dataset of Stephan and colleagues in the early 1980s, no major new comparative datasets covering multiple brain regions and a large number of primate species have become available. However, technological and other advances in the last two decades, particularly magnetic resonance imaging (MRI) and the creation of institutions devoted to the collection and preservation of rare brain specimens, provide opportunities to rectify this situation. Here, we present a new dataset including brain region volumetric measurements of 39 species, including 20 species not previously available in the literature, with measurements of 16 brain areas. These volumes were extracted from MRI of 46 brains of 38 species from the Netherlands Institute of Neuroscience Primate Brain Bank, scanned at high resolution with a 9.4-T scanner, plus a further 7 donated MRI of 4 primate species. Partial measurements were made on an additional 8 brains of 5 species. We make the dataset and MRI scans available online in the hope that they will be of value to researchers conducting comparative studies of primate evolution.

Henry Herbert Donaldson's (1857-1938) contribution to an organized approach to the experimental study of the mammalian central nervous system.

This article shows that the academic and research careers of Henry Herbert Donaldson (1857-1938) were directed to provide basic information about the growth of the vertebrate nervous system and to provide standards and the means to make such research efficient. He earned the reputation of making the albino rat a standard laboratory animal. His academic career began when he was an undergraduate at Yale University in 1875 and concluded with his death as Professor and Head of the Department of Neurology at the Wistar Institute of Anatomy and Biology of the University of Pennsylvania in 1938. During that period, pivotal experiences occurred, including research in physiological chemistry with Chittenden at the Sheffield School at Yale, graduate study at Johns Hopkins University, postgraduate study in Europe, and professorial positions at Clark University and the University of Chicago. It was at Johns Hopkins University that Donaldson learned about the need for physiological, anatomical, and psychophysical research and about the techniques to allow such research. It was at Clark University that he had first-hand and detailed experience with the anatomy of the brain of a deaf-blind-mute woman, as he attempted to correlate her sensory deficits with her brain development. It was at Clark University that he clearly recognized the need for standardization in neurological research. At the University of Chicago, he developed administrative skills and began a coordinated research effort to delimit the growth of the nervous system. It was at Chicago that he learned that the albino rat could be a reasonable subject for such research. It was also at Chicago that he was able to formulate ideas about the future organizational needs of human neuroanatomy. It was at the Wistar Institute that his research program and his professional career matured. He organized a research effort to elucidate the growth of the nervous system. He contributed to the coordination of neurological research in the United States and Europe. It was while at the Wistar Institute that he became well-known for making the albino rat a standard laboratory mammal-a convenient living material for research.

The National Undergraduate Neuroanatomy Competition: Five years of educating, inspiring and motivating our future neurologists and neurosurgeons

Neurological conditions are common so a knowledge of neuroanatomy is necessary for junior doctors. Additionally, some students have a particular interest in neuroscience. However, little time is dedicated to neuroanatomy in the medical curriculum, and many students struggle with neuroanatomy. The National Undergraduate Neuroanatomy Competition (NUNC) aims to support the development of neuroanatomical knowledge among medical students and promote interest in neurosciences. Students who attended the NUNC completed a series of neuroanatomy-based examinations and a questionnaire investigating aspects of neuroanatomy teaching and resources at their home university. 387 students attended the NUNC between 2013 and 2017, of which 382 had a complete data set (response rate 98.7%). Male students significantly outperformed female students (p<0.0001) and clinical students outperformed pre-clinical students (p<0.05). Best answered questions were on the spine (average score 53.9%), and the most poorly answered questions were on the vasculature (average score 44.7%). Students felt that the neuroanatomy teaching, time spent on neuroanatomy and dissection/prosection resources were all reasonable (6-7/10) at their home institution. Elearning resources were rated more poorly (5.4/10). We conclude that the NUNC gives students the opportunity to enhance their neuroanatomical knowledge and gives keen students the chance to develop their interest

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Técnicas actuales de reparación nerviosa / Current techniques in peripheral nerve repair

Las lesiones del sistema nervioso periférico son uno de los retos terapéuticos de nuestra especialidad, no sólo por la dificultad técnica e instrumental necesaria para resolverlas, sino por la importancia de sus secuelas y los pobres resultados obtenidos con una deficiente técnica quirúrgica. Para obtener un óptimo resultado, es preceptivo, no sólo realizar un correcto diagnóstico, sino además, conocer y dominar las distintas opciones terapéuticas. El objetivo de la presente revisión es abordar las distintas indicaciones y técnicas quirúrgicas usadas actualmente para el tratamiento de las lesiones nerviosas

The injuries of the peripheral nervous system are one of the therapeutic challenges in our speciality given their technical and instrumental difficulty, the importance of the disability and the few results obtained with a deficient surgical technique. For an optimum result, a correct diagnosis is needed as well as to know and to dominate the different therapeutics options. The objetive of the current review is to deal with the different indications and surgery techniques currently used for the treatment of the nervous injuries

Trastorno por estrés postraumático y cerebro / Posttraumatic stress disorder and brain

En la actualidad, encontramos numerosa bibliografía sobre las alteraciones estructurales y funcionales cerebrales en el Trastorno por Estrés Postraumático (TEPT). En este trabajo se presenta una revisión bibliográfica no sistemática de los artículos publicados en los últimos años sobre la neuroanatomía y la neurofisiología del Trastorno por Estrés Postraumático. Los objetivos son: describir las hipótesis que relacionan las alteraciones neuroanatómicas y la sintomatología característica del TEPT; y describir el perfil neuropsicológico y los tratamientos con base en las neurociencias, partiendo de la premisa de que las limitaciones metodológicas de los estudios no permiten generalizar estos resultados. Finalmente se propone que la rehabilitación neuropsicológica de los déficits cognitivos mostrados por estos pacientes potenciaría la eficacia de los tratamientos psicológicos (AU)

Currently, we have enough literature about brain findings in posttraumatic stress disorder (PTSD). A bibliographical review of the articles published in the last years related to neuroanatomy and neurophysiology of Posttraumatic Stress Disorder is presented. The aims of this review are: to describe the hypotheses that relate the neuroanatomics disorders and the typical symptomatology of the TEPT, and to describe the neuropsychological profile and the treatments based in Neuroscience, taking into account that the methodological limitations of the studies do not allow to generalize these results. Finally, we raise the rehabilitation of the neuropsychological cognitive deficits shown by these patients, with a view to enhancing the effectiveness of psychological treatments (AU)

Human chorioretinal layer thicknesses measured in macula-wide, high-resolution histologic sections.

PURPOSE: To provide a comprehensive description of chorioretinal layer thicknesses in the normal human macula, including two-layer pairs that can produce a combined signal in some optical coherence tomography (OCT) devices (ganglion cell [GCL] and inner plexiform [IPL] layers and outer plexiform [OPL] and outer nuclear [ONL] layers). METHODS: In 0.8-µm-thick, macula-wide sections through the foveola of 18 donors (age range, 40-92 years), 21 layers were measured at 25 locations by a trained observer and validated by a second observer. Tissue volume changes were assessed by comparing total retinal thickness in ex vivo OCT and in sections. RESULTS: Median tissue shrinkage was 14.5% overall and 29% in the fovea. Histologic laminar boundaries resembled those in SD-OCT scans, but the shapes of the foveolar OPL and ONL differed. Histologic GCL, IPL, and OPLHenle were thickest at 0.8. to 1, 1.5, and 0.4 mm eccentricity, respectively. ONL was thickest in an inward bulge at the foveal center. At 1 mm eccentricity, GCL, INL, and OPLHenle represented 17.3% to 21.1%, 18.0% to 18.5%, and 14.2% to 16.6% of total retinal thickness, respectively. In donors ≥ 70 years of age, the RPE and choroid were 17.1% and 29.6% thinner and OPLHenle was 20.8% thicker than in donors <70 years. CONCLUSIONS: In this study, the first graphic representation and thickness database of chorioretinal layers in normal macula were generated. Newer OCT systems can separate GCL from IPL and OPLHenle from ONL, with good agreement for the proportion of retinal thickness occupied by OPLHenle in OCT and histology. The thickening of OPLHenle in older eyes may reflect Müller cell hypertrophy associated with rod loss.

Standardized atlas of the brain of the desert locust, Schistocerca gregaria.

In order to understand the connectivity of neuronal networks, their constituent neurons should ideally be studied in a common framework. Since morphological data from physiologically characterized and stained neurons usually arise from different individual brains, this can only be performed in a virtual standardized brain that compensates for interindividual variability. The desert locust, Schistocerca gregaria, is an insect species used widely for the analysis of olfactory and visual signal processing, endocrine functions, and neural networks controlling motor output. To provide a common multi-user platform for neural circuit analysis in the brain of this species, we have generated a standardized three-dimensional brain of this locust. Serial confocal images from whole-mount locust brains were used to reconstruct 34 neuropil areas in ten brains. For standardization, we compared two different methods: an iterative shape-averaging (ISA) procedure by using affine transformations followed by iterative nonrigid registrations, and the Virtual Insect Brain (VIB) protocol by using global and local rigid transformations followed by local nonrigid transformations. Both methods generated a standard brain, but for different applications. Whereas the VIB technique was designed to visualize anatomical variability between the input brains, the purpose of the ISA method was the opposite, i.e., to remove this variability. A novel individually labeled neuron, connecting the lobula to the midbrain and deutocerebrum, has been registered into the ISA atlas and demonstrates its usefulness and accuracy for future analysis of neural networks. The locust standard brain is accessible at http://www.3d-insectbrain.com .

MorphML: level 1 of the NeuroML standards for neuronal morphology data and model specification.

Quantitative neuroanatomical data are important for the study of many areas of neuroscience, and the complexity of problems associated with neuronal structure requires that research from multiple groups across many disciplines be combined. However, existing neuron-tracing systems, simulation environments, and tools for the visualization and analysis of neuronal morphology data use a variety of data formats, making it difficult to exchange data in a readily usable way. The NeuroML project was initiated to address these issues, and here we describe an extensible markup language standard, MorphML, which defines a common data format for neuronal morphology data and associated metadata to facilitate data and model exchange, database creation, model publication, and data archiving. We describe the elements of the standard in detail and outline the mappings between this format and those used by a number of popular applications for reconstruction, simulation, and visualization of neuronal morphology.

The Virtual Insect Brain protocol: creating and comparing standardized neuroanatomy.

BACKGROUND: In the fly Drosophila melanogaster, new genetic, physiological, molecular and behavioral techniques for the functional analysis of the brain are rapidly accumulating. These diverse investigations on the function of the insect brain use gene expression patterns that can be visualized and provide the means for manipulating groups of neurons as a common ground. To take advantage of these patterns one needs to know their typical anatomy. RESULTS: This paper describes the Virtual Insect Brain (VIB) protocol, a script suite for the quantitative assessment, comparison, and presentation of neuroanatomical data. It is based on the 3D-reconstruction and visualization software Amira, version 3.x (Mercury Inc.) 1. Besides its backbone, a standardization procedure which aligns individual 3D images (series of virtual sections obtained by confocal microscopy) to a common coordinate system and computes average intensities for each voxel (volume pixel) the VIB protocol provides an elaborate data management system for data administration. The VIB protocol facilitates direct comparison of gene expression patterns and describes their interindividual variability. It provides volumetry of brain regions and helps to characterize the phenotypes of brain structure mutants. Using the VIB protocol does not require any programming skills since all operations are carried out at an intuitively usable graphical user interface. Although the VIB protocol has been developed for the standardization of Drosophila neuroanatomy, the program structure can be used for the standardization of other 3D structures as well. CONCLUSION: Standardizing brains and gene expression patterns is a new approach to biological shape and its variability. The VIB protocol provides a first set of tools supporting this endeavor in Drosophila. The script suite is freely available at http://www.neurofly.de2.

El dolor neuropático en la lepra

El dolor neuropático crónico en los pacientes de lepra ya tratados no es objeto de mucha atención. En este artículo se revisan los conceptos, características clínicas y el diagnóstico del dolor neuropático, y se exponen los posibles mecanismos patofisiológicos, dificultades de tratamiento y necesidades de investigación en esta área (AU)