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Parkinson's disease (PD) is characterized by the death of substantia nigra pars compacta (SNc) dopamine (DA) neurons, but the pathophysiological mechanisms that precede and drive their death remain unknown. The activity of DA neurons is likely altered in PD, but we understand little about if or how chronic changes in activity may contribute to degeneration. To address this question, we developed a chemogenetic (DREADD) mouse model to chronically increase DA neuron activity and confirmed this increase using ex vivo electrophysiology. Chronic hyperactivation of DA neurons resulted in prolonged increases in locomotor activity during the light cycle and decreases during the dark cycle, consistent with chronic changes in DA release and circadian disturbances. We also observed early, preferential degeneration of SNc projections, recapitulating the PD hallmarks of selective vulnerability of SNc axons and the comparative resilience of ventral tegmental area axons. This was followed by the eventual loss of midbrain DA neurons. Continuous DREADD activation resulted in a sustained increase in baseline calcium levels, supporting a role for increased calcium in the neurodegeneration process. Finally, spatial transcriptomics from DREADD mice examining midbrain DA neurons and striatal targets, and cross-validation with human patient samples, provided insights into potential mechanisms of hyperactivity-induced toxicity and PD. Our results thus reveal the preferential vulnerability of SNc DA neurons to increased neural activity and support a potential role for increased neural activity in driving degeneration in PD.
Pubmed ID: 40856691
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Neurolucida is advanced scientific software for brain mapping, neuron reconstruction, anatomical mapping, and morphometry. Since its debut more than 20 years ago, Neurolucida has continued to evolve and has become the worldwide gold-standard for neuron reconstruction and 3D mapping. Neurolucida has the flexibility to handle data in many formats: using live images from digital or video cameras; stored image sets from confocal microscopes, electron microscopes, and scanning tomographic sources, or through the microscope oculars using the patented LucividTM. Neurolucida controls a motorized XYZ stage for integrated navigation through tissue sections, allowing for sophisticated analysis from many fields-of-view. Neurolucidas Serial Section Manager integrates unlimited sections into a single data file, maintaining each section in aligned 3D space for full quantitative analysis. Neurolucidas neuron tracing capabilities include 3D measurement and reconstruction of branching processes. Neurolucida also features sophisticated tools for mapping delineate and map anatomical regions for detailed morphometric analyses. Neurolucida uses advanced computer-controlled microscopy techniques to obtain accurate results and speed your work. Plug-in modules are available for confocal and MRI analysis, 3D solid modeling, and virtual slide creation. The user-friendly interface gives you rapid results, allowing you to acquire data and capture the full 3D extent of neurons and brain regions. You can reconstruct neurons or create 3D serial reconstructions directly from slides or acquired images, and Neurolucida offers full microscope control for brightfield, fluorescent, and confocal microscopes. Its added compatibility with 64-bit Microsoft Vista enables reconstructions with even larger images, image stacks, and virtual slides. Adding the Solid Modeling Module allows you to rotate and view your reconstructions in real time. Neurolucida is available in two separate versions Standard and Workstation. The Standard version enables control of microscope hardware, whereas the Workstation version is used for offline analysis away from the microscope. Neurolucida provides quantitative analysis with results presented in graphical or spreadsheet format exportable to Microsoft Excel. Overall, features include: - Tracing Neurons - Anatomical Mapping - Image Processing and Analysis Features - Editing - Morphometric Analysis - Hardware Integration - Cell Analysis - Visualization Features Sponsors: Neurolucida is supported by MBF Bioscience.
View all literature mentionsNon-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsA commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.
View all literature mentionsGenome wide database of gene expression in mouse brain.
View all literature mentions3D reference atlas to use with online datasets or as standalone resources. Can be used to analyze, visualize, and integrate multimodal and multiscale datasets in 3D. Intensity and shape population average template brain serves as basis of reference space and coordinate system. Average was constructed at 10 um voxel resolution by interpolating high resolution serial two photon tomography images from young adult C57BL/6J mice. Using multimodal reference data, entire brain was directly parcellated in 3D, labeling every voxel with brain structure from Allen Mouse Reference Atlas Ontology. In the 2017 release, the parcellation spanned 43 isocortical areas and their layers, 329 subcortical gray matter structures, 81 fiber tracts, and 8 ventricular structures.
View all literature mentionsStereo Investigator system includes microscope, computer, and Stereo Investigator software. Software works with Brightfield, Multi-Channel Fluorescence, Confocal, and Structured Illumination Microscopes. System used to provide estimates of number, length, area, and volume of cells or biological structures in tissue specimen in areas of neuroscience including neurodegenerative diseases, neuropathy, memory, and behavior, pulmonary research, spinal cord research, and toxicology.
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis monoclonal targets Tyrosine Hydroxylase
View all literature mentionsThis unknown targets IgG (H+L)
View all literature mentionsThis polyclonal targets mCherry
View all literature mentionsThis polyclonal secondary targets IgY (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets DsRed
View all literature mentionsThis polyclonal targets Tyrosine Hydroxylase
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsDesktop application that provides interactive visualization functionality to analyze data from different 10x Genomics solutions. Used to interrogate different views of 10x data to gain insights into underlying biology.
View all literature mentionsSystem provides means to make quantification of number, length, area, and volume of cells, subcellular and macro structures in tissue specimens. Used to make discoveries in numerous areas of neuroscience, including neurodegenerative diseases, addiction, autism, neuropathy, memory, and behavior, as well as other research fields including pulmonary and kidney research, and toxicology.
View all literature mentionsMulti paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.
View all literature mentionsMus musculus with name B6.Cg-Igs7tm148.1(tetO-GCaMP6f.CAG-tTA2)Hze/J from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsVideo tracking software that tracks and analyzes the behavior, movement, and activity of any animal.
View all literature mentionsA web-based gene list enrichment analysis tool that provides various types of visualization summaries of collective functions of gene lists. It includes new gene-set libraries, an alternative approach to rank enriched terms, and various interactive visualization approaches to display enrichment results using the JavaScript library, Data Driven Documents (D3). The software can also be embedded into any tool that performs gene list analysis. System-wide profiling of genes and proteins in mammalian cells produce lists of differentially expressed genes / proteins that need to be further analyzed for their collective functions in order to extract new knowledge. Once unbiased lists of genes or proteins are generated from such experiments, these lists are used as input for computing enrichment with existing lists created from prior knowledge organized into gene-set libraries.
View all literature mentionsMus musculus with name B6.SJL-Slc6a3tm1.1(cre)Bkmn/J from IMSR.
View all literature mentionsA cloud-based collaborative platform which co-locates data, code, and computing resources for analyzing genome-scale data and seamlessly integrates these services allowing scientists to share and analyze data together. Synapse consists of a web portal integrated with the R/Bioconductor statistical package and will be integrated with additional tools. The web portal is organized around the concept of a Project which is an environment where you can interact, share data, and analysis methods with a specific group of users or broadly across open collaborations. Projects provide an organizational structure to interact with data, code and analyses, and to track data provenance. A project can be created by anyone with a Synapse account and can be shared among all Synapse users or restricted to a specific team. Public data projects include the Synapse Commons Repository (SCR) (syn150935) and the metaGenomics project (syn275039). The SCR provides access to raw data and phenotypic information for publicly available genomic data sets, such as GEO and TCGA. The metaGenomics project provides standardized preprocessed data and precomputed analysis of the public SCR data.
View all literature mentionsAllows monitoring of wireless wheel running activity without running wires.
View all literature mentionsVisium system allows to map whole transcriptome with morphological context in FFPE or fresh frozen tissues. Used to perform spatial transcriptomics, which combines histological information with whole transcriptome gene expression profiles to provide spatially resolved gene expression. System for classifying tissue based on total mRNA. Includes two software to analyze data. Space Ranger analysis software that automatically overlays spatial gene expression information on tissue image and identifies clusters of spots with similar transcription profiles. Loupe Browser visualization software to interactively explore results.
View all literature mentionsIntegrated commercial system comprising hardware, software and nCounter chemistry that enables simultaneous, highly multiplex spatial profiling of proteins or RNA in FFPE tissues. DSP platform quantifies abundance of protein or RNA by counting unique indexing oligonucleotides assigned to each target of interest. Used to rapidly and quantitatively assess biological implications of heterogeneity within tissue samples.
View all literature mentionsDevice connects wireless running wheels to data acquisition computer via a USB cable.All wheels must be set to the same address as the hub with which they communicate.Hub relays data to Wheel Manager Software.
View all literature mentionsCloud platform to be directly integrated in to the industry?s leading sequencing platforms, with no cumbersome and time consuming data transfer steps.
View all literature mentionsSoftware package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsSoftware application with data analysis tools and spreadsheet templates to track and visualize data. It is used to manage and process data.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsOptimized processor for fiber photometry.RZ5P is intended for use with TDT’s Synapse software.
View all literature mentionsOpen source and enterprise ready professional software for R statistical computing environment. Integrated development environment for R. Includes console, syntax highlighting editor that supports direct code execution, as well as tools for plotting, history, debugging and workspace management. Available in open source and commercial editions and runs on desktop Windows, Mac, and Linux or in browser connected to RStudio Server or RStudio Server Pro (Debian/Ubuntu, RedHat/CentOS, and SUSE Linux).
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