Synaptic Vesicles from Mammalian Brain: Large-Scale Purification and Physical and Immunochemical Characterization

1988 ◽  
Vol 50 (5) ◽  
pp. 1588-1596 ◽  
Author(s):  
E. Floor ◽  
S. F. Schaeffer ◽  
B. E. Feist ◽  
S. E. Leeman
Keyword(s):  
Synaptic Vesicles ◽  
Large Scale ◽  
Mammalian Brain ◽  
Immunochemical Characterization

scholarly journals Cocaine causes rapid remodeling of mesoaccumbens dopaminergic axons, synapses, and mitochondria

2021 ◽  
Author(s):  
Gregg Wildenberg ◽  
Anastasia Sorokina ◽  
Jessica Koranda ◽  
Alexis Monical ◽  
Chad Heer ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Large Scale ◽  
Drugs Of Abuse ◽  
Dopamine Neurons ◽  
Addictive Behaviors ◽  
Cell Type Specific ◽  
Genetic Labeling ◽  
Mitochondrial Elongation ◽  
First Time ◽  
Serial Electron Microscopy

Abstract Detailing the ways drugs of abuse physically alter dopaminergic circuits would provide new mechanisms for explaining addictive behaviors, future targets for therapeutic intervention, and insights into the nature of synaptic plasticity. We combine recent advances in genetic labeling with large volume serial electron microscopy to detail how normal dopaminergic (DA) axons interact with putative targets in the Nucleus Accumbens (NAc) and how those interactions change in mice briefly exposed to cocaine. We find that while most DA axonal boutons are devoid of obvious signs of synapses (i.e. synaptic vesicles or synaptic densities), many DA boutons physically interdigitate with dendrites or excitatory and inhibitory axons. A brief exposure to cocaine results in large-scale remodeling: extensive DA axonal branching and frequent occurrences of axonal blind-ended “bulbs”, filled with mitochondria and reminiscent of axonal retraction in the developing and damaged brain. The number of physical interdigitations and vesicle filled boutons in DA axons scales linearly with the length of axon in both controls and cocaine exposed animals and the size or the type of interaction (i.e. axo-axonic or axo-dendritic) do not change. Finally, we find in cocaine exposed animals, mitochondrial lengths are increased ~2.5 times relative to control. Mitochondrial elongation is cell type specific: primarily in DA neurons and downstream spiny dendrites, and localized to DA axons and not DA soma or dendrites. We show for the first time the effects of cocaine on remodeling of dopamine axon morphology and mitochondria and reveal new details on how dopamine neurons physically associate with downstream targets.

scholarly journals Sleep Spindles: Mechanisms and Functions

2020 ◽  
Vol 100 (2) ◽  
pp. 805-868 ◽  
Author(s):  
Laura M. J. Fernandez ◽  
Anita Lüthi
Keyword(s):  
Cognitive Abilities ◽  
Large Scale ◽  
Physiological State ◽  
Mammalian Brain ◽  
Sleep Spindles ◽  
Cognitive Profiles ◽  
Sleep Spindle ◽  
Discrete Events ◽  
Continuous Power ◽  
Electroencephalogram Eeg

Sleep spindles are burstlike signals in the electroencephalogram (EEG) of the sleeping mammalian brain and electrical surface correlates of neuronal oscillations in thalamus. As one of the most inheritable sleep EEG signatures, sleep spindles probably reflect the strength and malleability of thalamocortical circuits that underlie individual cognitive profiles. We review the characteristics, organization, regulation, and origins of sleep spindles and their implication in non-rapid-eye-movement sleep (NREMS) and its functions, focusing on human and rodent. Spatially, sleep spindle-related neuronal activity appears on scales ranging from small thalamic circuits to functional cortical areas, and generates a cortical state favoring intracortical plasticity while limiting cortical output. Temporally, sleep spindles are discrete events, part of a continuous power band, and elements grouped on an infraslow time scale over which NREMS alternates between continuity and fragility. We synthesize diverse and seemingly unlinked functions of sleep spindles for sleep architecture, sensory processing, synaptic plasticity, memory formation, and cognitive abilities into a unifying sleep spindle concept, according to which sleep spindles 1) generate neural conditions of large-scale functional connectivity and plasticity that outlast their appearance as discrete EEG events, 2) appear preferentially in thalamic circuits engaged in learning and attention-based experience during wakefulness, and 3) enable a selective reactivation and routing of wake-instated neuronal traces between brain areas such as hippocampus and cortex. Their fine spatiotemporal organization reflects NREMS as a physiological state coordinated over brain and body and may indicate, if not anticipate and ultimately differentiate, pathologies in sleep and neurodevelopmental, -degenerative, and -psychiatric conditions.

scholarly journals Emerging imaging methods to study whole-brain function in rodent models

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marija Markicevic ◽  
Iurii Savvateev ◽  
Christina Grimm ◽  
Valerio Zerbi
Keyword(s):  
Large Scale ◽  
Functional Organization ◽  
Imaging Techniques ◽  
Brain Activity ◽  
Research Question ◽  
Careful Consideration ◽  
Mammalian Brain ◽  
High Temporal Resolution ◽  
Imaging Methods ◽  
Evoked Activity

AbstractIn the past decade, the idea that single populations of neurons support cognition and behavior has gradually given way to the realization that connectivity matters and that complex behavior results from interactions between remote yet anatomically connected areas that form specialized networks. In parallel, innovation in brain imaging techniques has led to the availability of a broad set of imaging tools to characterize the functional organization of complex networks. However, each of these tools poses significant technical challenges and faces limitations, which require careful consideration of their underlying anatomical, physiological, and physical specificity. In this review, we focus on emerging methods for measuring spontaneous or evoked activity in the brain. We discuss methods that can measure large-scale brain activity (directly or indirectly) with a relatively high temporal resolution, from milliseconds to seconds. We further focus on methods designed for studying the mammalian brain in preclinical models, specifically in mice and rats. This field has seen a great deal of innovation in recent years, facilitated by concomitant innovation in gene-editing techniques and the possibility of more invasive recordings. This review aims to give an overview of currently available preclinical imaging methods and an outlook on future developments. This information is suitable for educational purposes and for assisting scientists in choosing the appropriate method for their own research question.

scholarly journals A platform for brain-wide imaging and reconstruction of individual neurons

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Michael N Economo ◽  
Nathan G Clack ◽  
Luke D Lavis ◽  
Charles R Gerfen ◽  
Karel Svoboda ◽  
...  
Keyword(s):  
Long Range ◽  
High Speed ◽  
Large Scale ◽  
Three Dimensional ◽  
Image Data ◽  
Mammalian Brain ◽  
Projection Neurons ◽  
Computational Tools ◽  
Two Photon ◽  
Axonal Arbors

The structure of axonal arbors controls how signals from individual neurons are routed within the mammalian brain. However, the arbors of very few long-range projection neurons have been reconstructed in their entirety, as axons with diameters as small as 100 nm arborize in target regions dispersed over many millimeters of tissue. We introduce a platform for high-resolution, three-dimensional fluorescence imaging of complete tissue volumes that enables the visualization and reconstruction of long-range axonal arbors. This platform relies on a high-speed two-photon microscope integrated with a tissue vibratome and a suite of computational tools for large-scale image data. We demonstrate the power of this approach by reconstructing the axonal arbors of multiple neurons in the motor cortex across a single mouse brain.

scholarly journals Inferring cortical function in the mouse visual system through large-scale systems neuroscience

2016 ◽  
Vol 113 (27) ◽  
pp. 7337-7344 ◽  
Author(s):  
Michael Hawrylycz ◽  
Costas Anastassiou ◽  
Anton Arkhipov ◽  
Jim Berg ◽  
Michael Buice ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Large Scale ◽  
Model Organism ◽  
Building Blocks ◽  
Mammalian Brain ◽  
Cortical Function ◽  
Scientific Mission ◽  
Large Populations ◽  
Cell Type Specific ◽  
And Behavior

The scientific mission of the Project MindScope is to understand neocortex, the part of the mammalian brain that gives rise to perception, memory, intelligence, and consciousness. We seek to quantitatively evaluate the hypothesis that neocortex is a relatively homogeneous tissue, with smaller functional modules that perform a common computational function replicated across regions. We here focus on the mouse as a mammalian model organism with genetics, physiology, and behavior that can be readily studied and manipulated in the laboratory. We seek to describe the operation of cortical circuitry at the computational level by comprehensively cataloging and characterizing its cellular building blocks along with their dynamics and their cell type-specific connectivities. The project is also building large-scale experimental platforms (i.e., brain observatories) to record the activity of large populations of cortical neurons in behaving mice subject to visual stimuli. A primary goal is to understand the series of operations from visual input in the retina to behavior by observing and modeling the physical transformations of signals in the corticothalamic system. We here focus on the contribution that computer modeling and theory make to this long-term effort.

scholarly journals Author response: Rapid purification and metabolomic profiling of synaptic vesicles from mammalian brain

2020 ◽  
Author(s):  
Lynne Chantranupong ◽  
Jessica L Saulnier ◽  
Wengang Wang ◽  
Drew R Jones ◽  
Michael E Pacold ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Author Response ◽  
Mammalian Brain ◽  
Metabolomic Profiling ◽  
Rapid Purification

scholarly journals Large-scale voltage imaging in the brain using targeted illumination

2021 ◽  
Author(s):  
Sheng Xiao ◽  
Eric Lowet ◽  
Howard Gritton ◽  
Pierre Fabris ◽  
Yangyang Wang ◽  
...  
Keyword(s):  
High Speed ◽  
Large Scale ◽  
Low Cost ◽  
Mammalian Brain ◽  
Voltage Imaging ◽  
Background Rejection ◽  
Large Scale Network ◽  
Voltage Signal ◽  
Signal Contrast ◽  
The Brain

Recent improvements in genetically encoded voltage indicators enabled high precision imaging of single neuron's action potentials and subthreshold membrane voltage dynamics in the mammalian brain. To perform high speed voltage imaging, widefield microscopy remains an essential tool to record activity from many neurons simultaneously over a large anatomical area. However, the lack of optical sectioning makes widefield microscopy prone to background signal contamination. We implemented a simple, low cost, targeted illumination strategy based on a digital micromirror device (DMD) to restrict illumination to the cells of interest to improve background rejection, and quantified optical voltage signal improvement in neurons expressing the fully genetically encoded voltage indicator SomArchon. We found that targeted illumination, in comparison to widefield illumination, increased SomArchon signal contrast and reduced background cross-contamination in the brains of awake mice. Such improvement permitted the reduction of illumination intensity, and thus reduced fluorescence photobleaching and prolonged imaging duration. When coupled with a high-speed sCMOS camera, we routinely imaged tens of spiking neurons simultaneously over several minutes in the brain. Thus, the DMD-based targeted illumination strategy described here offers a simple solution for high-speed voltage imaging analysis of large scale network at the millisecond time scale with single cell resolution in the brains of behaving animals.

scholarly journals Amyloid conformers of the FXR1 protein prevent mRNA degradation in cortical neurons

2019 ◽  
Author(s):  
J.V. Sopova ◽  
E. I Koshel ◽  
T.A. Belashova ◽  
S.P. Zadorsky ◽  
A.V. Sergeeva ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Large Scale ◽  
Amyloid Fibrils ◽  
Mammalian Species ◽  
Rnase A ◽  
Mammalian Brain ◽  
Polarization Microscopy ◽  
Proteomic Approach ◽  
Functional Amyloids

AbstractFunctional amyloids regulate vital processes in a variety of organisms from bacteria to higher eukaryotes. The development of methods enabling large-scale screening for amyloids opens up opportunity for systemic analysis of the prevalence of amyloids in nature. Using an original proteomic approach, we identified several proteins forming amyloid-like detergent-resistant aggregates in the rat brain. One of them is the FXR1 protein, which is known to regulate memory and emotions (1, 2). We demonstrated that in brain FXR1 forms amyloid oligomers and insoluble detergent-resistant aggregates that strongly colocalize with amyloid-specific dye Thioflavin S and bind mRNA molecules. Moreover, we demonstrated that mRNAs colocalized with FXR1 amyloid particles are completely resistant to treatment with RNAse A. Taking into consideration that the members of ribonuclease A superfamily function in neurons (3) we can conclude that amyloid conformers of FXR1 control RNA stability in brain. Thus, in contrast to pathological amyloids that cause neurodegeneration, FXR1 is the functional amyloid in forebrain. We showed that amyloid properties of FXR1 depend on its N-terminal part from 1 to 379 amino acids. This fragment forms amyloid fibrils in vitro that bind Congo red and manifest apple-green birefringence when assayed by polarization microscopy. The amyloid-forming region of FXR1 is highly conserved in mammals. These data suggest that the ability of amyloid conformers of FXR1 to protect mRNAs is characteristic of different mammalian species, including humans.Significance StatementAmyloids are highly ordered cross-β sheet protein fibrils associated with many neurodegenerative diseases including Alzheimer’s disease. However, some amyloid proteins regulate vital processes. We identified a set of proteins that form amyloid-like aggregates in the brain of healthy rats. One of them - the FXR1 protein is known to regulate memory and emotions. FXR1 forms amyloid fibrils that bind RNA molecules and prevent their degradation in brain cortex neurons. Amyloid-forming sequence of FXR1 is highly conserved across mammals including human. Discovery of functional amyloids in mammalian brain shows that strategy aimed at the development of universal anti-amyloid drugs is unpromising. Such potential drugs should prevent or suppress formation of pathological aggregates of a certain protein, but not affect functional amyloids.

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