Long-term potentiation of synaptic transmission in the hippocampus is the primary experimental model for investigating the synaptic basis of learning and memory in vertebrates. The best understood form of long-term potentiation is induced by the activation of the N-methyl-D-aspartate receptor complex. This subtype of glutamate receptor endows long-term potentiation with Hebbian characteristics, and allows electrical events at the postsynaptic membrane to be transduced into chemical signals which, in turn, are thought to activate both pre- and postsynaptic mechanisms to generate a persistent increase in synaptic strength.

A synaptic model of memory: long-term potentiation in the hippocampus

▪ Abstract Synaptic transmission is a dynamic process. Postsynaptic responses wax and wane as presynaptic activity evolves. This prominent characteristic of chemical synaptic transmission is a crucial determinant of the response properties of synapses and, in turn, of the stimulus properties selected by neural networks and of the patterns of activity generated by those networks. This review focuses on synaptic changes that result from prior activity in the synapse under study, and is restricted to short-term effects that last for at most a few minutes. Forms of synaptic enhancement, such as facilitation, augmentation, and post-tetanic potentiation, are usually attributed to effects of a residual elevation in presynaptic [Ca2+]i, acting on one or more molecular targets that appear to be distinct from the secretory trigger responsible for fast exocytosis and phasic release of transmitter to single action potentials. We discuss the evidence for this hypothesis, and the origins of the different kinetic phases...

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Short-Term Synaptic Plasticity

This work was supported by grants from the National Institutes of Health (R01 AG048814, B.A.B.; RO1 DA15043, B.A.B.; P50 NS38377, V.L.D. and T.M.D.) Christopher and Dana Reeve Foundation (B.A.B.), the Novartis Institute for Biomedical Research (B.A.B.), Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (B.A.B.), the JPB Foundation (B.A.B., T.M.D.), the Cure Alzheimer’s Fund (B.A.B.), the Glenn Foundation (B.A.B.), the Esther B O’Keeffe Charitable Foundation (B.A.B.), the Maryland Stem Cell Research Fund (2013-MSCRFII-0105-00, V.L.D.; 2012-MSCRFII-0268-00, T.M.D.; 2013-MSCRFII-0105-00, T.M.D.; 2014-MSCRFF-0665, M.K.). S.A.L. was supported by a postdoctoral fellowship from the Australian National Health and Medical Research Council (GNT1052961), and the Glenn Foundation Glenn Award. L.E.C. was funded by a Merck Research Laboratories postdoctoral fellowship (administered by the Life Science Research Foundation). W.-S.C. was supported by a career transition grant from NEI (K99EY024690). C.J.B. was supported by a postdoctoral fellowship from Damon Runyon Cancer Research Foundation (DRG-2125-12). L.S. was supported by a postdoctoral fellowship from the German Research Foundation (DFG, SCHI 1330/1-1).

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Neurotoxic reactive astrocytes are induced by activated microglia

Foundations of Confocal Scanned Imaging in Light Microscopy -- Fundamental Limits in Confocal Microscopy -- Special Optical Elements -- Points, Pixels, and Gray Levels: Digitizing Image Data -- Laser Sources for Confocal Microscopy -- Non-Laser Light Sources for Three-Dimensional Microscopy -- Objective Lenses for Confocal Microscopy -- The Contrast Formation in Optical Microscopy -- The Intermediate Optical System of Laser-Scanning Confocal Microscopes -- Disk-Scanning Confocal Microscopy -- Measuring the Real Point Spread Function of High Numerical Aperture Microscope Objective Lenses -- Photon Detectors for Confocal Microscopy -- Structured Illumination Methods -- Visualization Systems for Multi-Dimensional Microscopy Images -- Automated Three-Dimensional Image Analysis Methods for Confocal Microscopy -- Fluorophores for Confocal Microscopy: Photophysics and Photochemistry -- Practical Considerations in the Selection and Application of Fluorescent Probes -- Guiding Principles of Specimen Preservation for Confocal Fluorescence Microscopy -- Confocal Microscopy of Living Cells -- Aberrations in Confocal and Multi-Photon Fluorescence Microscopy Induced by Refractive Index Mismatch -- Interaction of Light with Botanical Specimens -- Signal-to-Noise Ratio in Confocal Microscopes -- Comparison of Widefield/Deconvolution and Confocal Microscopy for Three-Dimensional Imaging -- Blind Deconvolution -- Image Enhancement by Deconvolution -- Fiber-Optics in Scanning Optical Microscopy -- Fluorescence Lifetime Imaging in Scanning Microscopy -- Multi-Photon Molecular Excitation in Laser-Scanning Microscopy -- Multifocal Multi-Photon Microscopy -- 4Pi Microscopy -- Nanoscale Resolution with Focused Light: Stimulated Emission Depletion and Other Reversible Saturable Optical Fluorescence Transitions Microscopy Concepts -- Mass Storage, Display, and Hard Copy -- Coherent Anti-Stokes Raman Scattering Microscopy -- Related Methods for Three-Dimensional Imaging -- Tutorial on Practical Confocal Microscopy and Use of the Confocal Test Specimen -- Practical Confocal Microscopy -- Selective Plane Illumination Microscopy -- Cell Damage During Multi-Photon Microscopy -- Photobleaching -- Nonlinear (Harmonic Generation) Optical Microscopy -- Imaging Brain Slices -- Fluorescent Ion Measurement -- Confocal and Multi-Photon Imaging of Living Embryos -- Imaging Plant Cells -- Practical Fluorescence Resonance Energy Transfer or Molecular Nanobioscopy of Living Cells -- Automated Confocal Imaging and High-Content Screening for Cytomics -- Automated Interpretation of Subcellular Location Patterns from Three-Dimensional Confocal Microscopy -- Display and Presentation Software -- When Light Microscope Resolution Is Not Enough:Correlational Light Microscopy and Electron Microscopy -- Databases for Two- and Three-Dimensional Microscopical Images in Biology -- Confocal Microscopy of Biofilms — Spatiotemporal Approaches -- Bibliography of Confocal Microscopy.

Handbook of biological confocal microscopy

Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions.

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Astrocytes: biology and pathology

Transcriptomic evidence for dense peptidergic networks within forebrains of four widely divergent tetrapods.

Corrigendum: NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones

Seeking new insights into intracortical neuromodulation, we have analyzed results from deep RNA-Seq analysis of 22,439 individual mouse neocortical neurons. With special interest in ways that cortical neurons may use paracrine neuropeptide (NP) signaling to modulate one anothers9 synaptic and electrical function, we have concentrated on neocortical expression of genes encoding 18 neuropeptide precursor proteins (NPPs) and 29 cognate G-protein-coupled neuropeptide receptors (NP-GPCRs). We find that over 97% of sampled neurons express at least one of these NPP genes and that 98% express at least one NP-GPCR gene, with almost all neurons expressing several genes in each category. Reference to a transcriptomic taxonomy suggests that neocortical neuron types should be distinguishable by unique combinatorial signatures of NPP and NP-GPCR expression. We use these neuron-type-specific NP expression signatures to generate testable predictions regarding dense peptidergic neuromodulatory networks that may play prominent roles in cortical activity homeostasis and memory engram storage.

Transcriptomic evidence for dense peptidergic neuromodulation networks in mouse cortex

Serial section Electron Microscopy can produce high throughput imaging of large biological specimen volumes. The high-resolution images are necessary to reconstruct dense neural wiring diagrams in the brain, so called connectomes. A high fidelity volume assembly is required to correctly reconstruct neural anatomy and synaptic connections. It involves seamless 2D stitching of the images within a serial section followed by 3D alignment of the stitched sections. The high throughput of ssEM necessitates 2D stitching to be done at the pace of imaging, which currently produces tens of terabytes per day. To achieve this, we present a modular volume assembly software pipeline ASAP(Assembly Stitching and Alignment Pipeline) that is scalable and parallelized to work with distributed systems. The pipeline is built on top of the Render [18] services used in the volume assembly of the brain of adult Drosophila melanogaster [2]. It achieves high throughput by operating on the meta-data and transformations of each image stored in a database, thus eliminating the need to render intermediate output. The modularity of ASAP allows for easy adaptation to new algorithms without significant changes to the workflow. The software pipeline includes a complete set of tools to do stitching, automated quality control, 3D section alignment, and rendering of the assembled volume to disk. We also implemented a workflow engine that executes the volume assembly workflow in an automated fashion triggered following the transfer of raw data. ASAP has been successfully utilized for continuous processing of several large-scale datasets of the mouse visual cortex and human brain samples including one cubic millimeter of mouse visual cortex [1, 25]. The pipeline also has multi-channel processing capabilities and can be applied to fluorescence and multi-modal datasets like array tomography.

https://biorxiv.org/content/10.1101/2021.11.24.469932v1.full.pdf

Stephen J. Smith

Papers

Transcriptomic evidence for dense peptidergic networks within forebrains of four widely divergent tetrapods.

Corrigendum: NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones

Transcriptomic evidence for dense peptidergic neuromodulation networks in mouse cortex

A Scalable and Modular Automated Pipeline for Stitching of Large Electron Microscopy Datasets

Polychromator for recording optical absorbance changes from single cells.