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The mechanism of rapid energy supply to the brain, especially to accommodate the heightened metabolic activity of excited states, is not well-understood. We explored the role of glycogen as a fuel source for neuromodulation using the noradrenergic stimulation of glia in a computational model of the neural-glial-vasculature ensemble (NGV). The detection of norepinephrine (NE) by the astrocyte and the coupled cAMP signal are rapid and largely insensitive to the distance of the locus coeruleus projection release sites from the glia, implying a diminished impact for volume transmission in high affinity receptor transduction systems. Glucosyl-conjugated units liberated from glial glycogen by NE-elicited cAMP second messenger transduction winds sequentially through the glycolytic cascade, generating robust increases in NADH and ATP before pyruvate is finally transformed into lactate. This astrocytic lactate is rapidly exported by monocarboxylate transporters to the associated neuron, demonstrating that the astrocyte-to-neuron lactate shuttle activated by glycogenolysis is a likely fuel source for neuromodulation and enhanced neural activity. Altogether, the energy supply for both astrocytes and neurons can be supplied rapidly by glycogenolysis upon neuromodulatory stimulus. [ABSTRACT FROM AUTHOR]

ABSTRACT Advances in the application of electron microscopy (EM) to serial imaging are opening doors to new ways of analyzing cellular structure. New and improved algorithms and workflows for manual and semiautomated segmentation allow us to observe the spatial arrangement of the smallest cellular features with unprecedented detail in full three-dimensions. From larger samples, higher complexity models can be generated; however, they pose new challenges to data management and analysis. Here we review some currently available solutions and present our approach in detail. We use the fully immersive virtual reality (VR) environment CAVE (cave automatic virtual environment), a room in which we are able to project a cellular reconstruction and visualize in 3D, to step into a world created with Blender, a free, fully customizable 3D modeling software with NeuroMorph plug-ins for visualization and analysis of EM preparations of brain tissue. Our workflow allows for full and fast reconstructions of volumes of brain neuropil using ilastik, a software tool for semiautomated segmentation of EM stacks. With this visualization environment, we can walk into the model containing neuronal and astrocytic processes to study the spatial distribution of glycogen granules, a major energy source that is selectively stored in astrocytes. The use of CAVE was key to the observation of a nonrandom distribution of glycogen, and led us to develop tools to quantitatively analyze glycogen clustering and proximity to other subcellular features. J. Comp. Neurol. 524:23-38, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Building on the pioneering efforts of Professor Huisman, several different databases of hemoglobin variants have been developed, each with progressively increased capacity for sophisticated queries and prompt updating. These resources are reviewed in the context of a larger plan for providing related resources on hemoglobins, benign and pathological variation in these proteins and the genes that encode them, and the regulation of the globin genes. [ABSTRACT FROM AUTHOR]

• We have reconstructed for the first time 4 cellular morphologies of astrocytes. • Reconstruction of 4 neurons, 4 microglia and 4 pericytes. • Neurons have larger but lesser dense volume compared to other nuclei. • Pericytes have the highest surface-area-to-volume ratio, together with astrocytes. • Mitochondria is distributed along the processes rather than the soma in all cells. With the rapid evolution in the automation of serial electron microscopy in life sciences, the acquisition of terabyte-sized datasets is becoming increasingly common. High resolution serial block-face imaging (SBEM) of biological tissues offers the opportunity to segment and reconstruct nanoscale structures to reveal spatial features previously inaccessible with simple, single section, two-dimensional images. In particular, we focussed here on glial cells, whose reconstruction efforts in literature are still limited, compared to neurons. We imaged a 750,000 cubic micron volume of the somatosensory cortex from a juvenile P14 rat, with 20 nm accuracy. We recognized a total of 186 cells using their nuclei, and classified them as neuronal or glial based on features of the soma and the processes. We reconstructed for the first time 4 almost complete astrocytes and neurons, 4 complete microglia and 4 complete pericytes, including their intracellular mitochondria, 186 nuclei and 213 myelinated axons. We then performed quantitative analysis on the three-dimensional models. Out of the data that we generated, we observed that neurons have larger nuclei, which correlated with their lesser density, and that astrocytes and pericytes have a higher surface to volume ratio, compared to other cell types. All reconstructed morphologies represent an important resource for computational neuroscientists, as morphological quantitative information can be inferred, to tune simulations that take into account the spatial compartmentalization of the different cell types. [ABSTRACT FROM AUTHOR]

ABSTRACT Advances in the application of electron microscopy (EM) to serial imaging are opening doors to new ways of analyzing cellular structure. New and improved algorithms and workflows for manual and semiautomated segmentation allow us to observe the spatial arrangement of the smallest cellular features with unprecedented detail in full three-dimensions. From larger samples, higher complexity models can be generated; however, they pose new challenges to data management and analysis. Here we review some currently available solutions and present our approach in detail. We use the fully immersive virtual reality (VR) environment CAVE (cave automatic virtual environment), a room in which we are able to project a cellular reconstruction and visualize in 3D, to step into a world created with Blender, a free, fully customizable 3D modeling software with NeuroMorph plug-ins for visualization and analysis of EM preparations of brain tissue. Our workflow allows for full and fast reconstructions of volumes of brain neuropil using ilastik, a software tool for semiautomated segmentation of EM stacks. With this visualization environment, we can walk into the model containing neuronal and astrocytic processes to study the spatial distribution of glycogen granules, a major energy source that is selectively stored in astrocytes. The use of CAVE was key to the observation of a nonrandom distribution of glycogen, and led us to develop tools to quantitatively analyze glycogen clustering and proximity to other subcellular features. J. Comp. Neurol. 524:23-38, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]