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

2020 ◽  
Author(s):  
G.A. Wildenberg ◽  
A.M. Sorokina ◽  
J.L. Koranda ◽  
A. Monical ◽  
C. 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

SummaryDetailing 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 Partial connectomes of labeled dopaminergic circuits reveal non-synaptic communication and axonal remodeling after exposure to cocaine

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Gregg Wildenberg ◽  
Anastasia Sorokina ◽  
Jessica Koranda ◽  
Alexis Monical ◽  
Chad Heer ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Large Scale ◽  
Drug Exposure ◽  
Cocaine Exposure ◽  
Cell Type ◽  
Major Locus ◽  
Anatomical Plasticity ◽  
Before And After ◽  
Cell Type Specific ◽  
Serial Electron Microscopy

Dopaminergic (DA) neurons exert profound influences on behavior including addiction. However, how DA axons communicate with target neurons and how those communications change with drug exposure remains poorly understood. We leverage cell type-specific labeling with large volume serial electron microscopy to detail DA connections in the nucleus accumbens (NAc) of the mouse (Mus musculus) before and after exposure to cocaine. We find that individual DA axons contain different varicosity types based on their vesicle contents. Spatially ordering along individual axons further suggests that varicosity types are non-randomly organized. DA axon varicosities rarely make specific synapses (<2%, 6/410), but instead are more likely to form spinule-like structures (15%, 61/410) with neighboring neurons. Days after a brief exposure to cocaine, DA axons were extensively branched relative to controls, formed blind-ended ‘bulbs’ filled with mitochondria, and were surrounded by elaborated glia. Finally, mitochondrial lengths increased by ~2.2 times relative to control only in DA axons and NAc spiny dendrites after cocaine exposure. We conclude that DA axonal transmission is unlikely to be mediated via classical synapses in the NAc and that the major locus of anatomical plasticity of DA circuits after exposure to cocaine are large-scale axonal re-arrangements with correlated changes in mitochondria.

Scheming

2018 ◽  
Author(s):  
Seán Damer
Keyword(s):  
Social Class ◽  
Housing Policy ◽  
Large Scale ◽  
Class Structure ◽  
Local Council ◽  
Housing Scheme ◽  
Post War ◽  
First Time ◽  
The Voice ◽  
House Building

This book seeks to explain how the Corporation of Glasgow, in its large-scale council house-building programme in the inter- and post-war years, came to reproduce a hierarchical Victorian class structure. The three tiers of housing scheme which it constructed – Ordinary, Intermediate, and Slum-Clearance – effectively signified First, Second and Third Class. This came about because the Corporation uncritically reproduced the offensive and patriarchal attitudes of the Victorian bourgeoisie towards the working-class. The book shows how this worked out on the ground in Glasgow, and describes the attitudes of both authoritarian housing officials, and council tenants. This is the first time the voice of Glasgow’s council tenants has been heard. The conclusion is that local council housing policy was driven by unapologetic considerations of social class.

Neuronal mRNA Translation in Addiction

2018 ◽  
Author(s):  
Emma Puighermanal ◽  
Emmanuel Valjent
Keyword(s):  
Structural Changes ◽  
Drugs Of Abuse ◽  
Mrna Translation ◽  
Cell Types ◽  
Behavioral Changes ◽  
Translational Machinery ◽  
Addictive Drugs ◽  
Specific Mrnas ◽  
Cell Type Specific ◽  
Future Work

Addictive drugs trigger persistent synaptic and structural changes in the neuronal reward circuits that are thought to underlie the development of drug-adaptive behavior. While transcriptional and epigenetic modifications are known to contribute to these circuit changes, accumulating evidence indicates that altered mRNA translation is also a key molecular mechanism. This chapter reviews recent studies demonstrating how addictive drugs alter protein synthesis and/or the translational machinery and how this leads to neuronal circuit remodeling and behavioral changes. Future work will determine precisely which neuronal circuits and cell types participate in these changes. The chapter summarizes current methodologies for identifying cell type-specific mRNAs whose translation is affected by drugs of abuse and gives recent examples of the mechanistic insights into addiction they provide.

scholarly journals Shell-crossing in a ΛCDM Universe

2020 ◽  
Vol 501 (1) ◽  
pp. L71-L75
Author(s):  
Cornelius Rampf ◽  
Oliver Hahn
Keyword(s):  
Dark Matter ◽  
Perturbation Theory ◽  
Large Scale ◽  
Cold Dark Matter ◽  
Three Dimensional ◽  
Random Initial Data ◽  
Recursion Relations ◽  
Indispensable Tool ◽  
First Time ◽  
Very High

ABSTRACT Perturbation theory is an indispensable tool for studying the cosmic large-scale structure, and establishing its limits is therefore of utmost importance. One crucial limitation of perturbation theory is shell-crossing, which is the instance when cold-dark-matter trajectories intersect for the first time. We investigate Lagrangian perturbation theory (LPT) at very high orders in the vicinity of the first shell-crossing for random initial data in a realistic three-dimensional Universe. For this, we have numerically implemented the all-order recursion relations for the matter trajectories, from which the convergence of the LPT series at shell-crossing is established. Convergence studies performed at large orders reveal the nature of the convergence-limiting singularities. These singularities are not the well-known density singularities at shell-crossing but occur at later times when LPT already ceased to provide physically meaningful results.

3.17% efficient Cu2ZnSnS4–BiVO4 integrated tandem cell for standalone overall solar water splitting

2021 ◽  
Author(s):  
Dingwang Huang ◽  
Kang Wang ◽  
Lintao Li ◽  
Kuang Feng ◽  
Na An ◽  
...  
Keyword(s):  
Water Splitting ◽  
Large Scale ◽  
Tandem Cell ◽  
Solar Water ◽  
Solar Water Splitting ◽  
First Time

3.17% efficient Cu2ZnSnS4–BiVO4 integrated tandem cell and a large scale 5 × 5 cm integrated CZTS–BiVO4 tandem device for standalone overall solar water splitting was assembled for the first time.

scholarly journals The SAMI Galaxy Survey: the third and final data release

2021 ◽  
Author(s):  
Scott M Croom ◽  
Matt S Owers ◽  
Nicholas Scott ◽  
Henry Poetrodjojo ◽  
Brent Groves ◽  
...  
Keyword(s):  
Large Scale ◽  
Resolving Power ◽  
Stellar Kinematics ◽  
New Era ◽  
Optical Wavelength ◽  
Astronomical Optics ◽  
Data Release ◽  
Gas Ionization ◽  
Release Data ◽  
First Time

Abstract We have entered a new era where integral-field spectroscopic surveys of galaxies are sufficiently large to adequately sample large-scale structure over a cosmologically significant volume. This was the primary design goal of the SAMI Galaxy Survey. Here, in Data Release 3 (DR3), we release data for the full sample of 3068 unique galaxies observed. This includes the SAMI cluster sample of 888 unique galaxies for the first time. For each galaxy, there are two primary spectral cubes covering the blue (370–570 nm) and red (630–740 nm) optical wavelength ranges at spectral resolving power of R = 1808 and 4304 respectively. For each primary cube, we also provide three spatially binned spectral cubes and a set of standardized aperture spectra. For each galaxy, we include complete 2D maps from parameterized fitting to the emission-line and absorption-line spectral data. These maps provide information on the gas ionization and kinematics, stellar kinematics and populations, and more. All data are available online through Australian Astronomical Optics (AAO) Data Central.

scholarly journals A Novel and Efficient High-Yield Method for Preparing Bacterial Ghosts

Toxins ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 420
Author(s):  
Yi Ma ◽  
Liu Cui ◽  
Meng Wang ◽  
Qiuli Sun ◽  
Kaisheng Liu ◽  
...  
Keyword(s):  
Large Scale ◽  
Expression System ◽  
High Yield ◽  
Wild Type ◽  
High Quality ◽  
Efficient Protection ◽  
Bacterial Ghosts ◽  
Cell Envelopes ◽  
Extracellular Structures ◽  
First Time

Bacterial ghosts (BGs) are empty cell envelopes possessing native extracellular structures without a cytoplasm and genetic materials. BGs are proposed to have significant prospects in biomedical research as vaccines or delivery carriers. The applications of BGs are often limited by inefficient bacterial lysis and a low yield. To solve these problems, we compared the lysis efficiency of the wild-type protein E (EW) from phage ΦX174 and the screened mutant protein E (EM) in the Escherichia coli BL21(DE3) strain. The results show that the lysis efficiency mediated by protein EM was improved. The implementation of the pLysS plasmid allowed nearly 100% lysis efficiency, with a high initial cell density as high as OD600 = 2.0, which was higher compared to the commonly used BG preparation method. The results of Western blot analysis and immunofluorescence indicate that the expression level of protein EM was significantly higher than that of the non-pLysS plasmid. High-quality BGs were observed by SEM and TEM. To verify the applicability of this method in other bacteria, the T7 RNA polymerase expression system was successfully constructed in Salmonella enterica (S. Enterica, SE). A pET vector containing EM and pLysS were introduced to obtain high-quality SE ghosts which could provide efficient protection for humans and animals. This paper describes a novel and commonly used method to produce high-quality BGs on a large scale for the first time.

Offshore Claims and Problems in the North Sea

1965 ◽  
Vol 59 (3) ◽  
pp. 505-522 ◽  
Author(s):  
Richard Young
Keyword(s):  
North Sea ◽  
Large Scale ◽  
Geneva Convention ◽  
Legal Principles ◽  
The North ◽  
Legal Problems ◽  
The North Sea ◽  
The Subject ◽  
First Time ◽  
Economic Considerations

The possible presence of very large petroleum and natural gas reserves in the area beneath the North Sea is currently the subject of intense investigation. If confirmed, as seems likely in at least some localities, this occurrence will raise legal problems of considerable interest and complexity. For the North Sea is not merely an oilfield covered by water: for centuries it has been one of the world's major fishery regions and the avenue to and from the world's busiest seaports. Thus all three of the present principal uses of the sea—fishing, navigation, and the exploitation of submarine resources—promise to meet for the first time on a large scale in an area where all are of major importance. The process of reconciling the various interests at stake will provide the first thoroughgoing test of the adequacy and acceptability of the general principles laid down in the 1958 Geneva Convention on the Continental Shelf and should add greatly to the practice and precedents available in this developing branch of the law. In the present article an attempt is made to review some of the geographical and economic considerations involved in the North Sea situation, to note some of the technical and legal developments that have already taken place, and to consider these elements in the light of the various interests and legal principles concerned.

scholarly journals Revealing the constituents of Egypt’s oldest beer using infrared and mass spectrometry

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mohamed A. Farag ◽  
Moamen M. Elmassry ◽  
Masahiro Baba ◽  
Renée Friedman
Keyword(s):  
Large Scale ◽  
Beer Brewing ◽  
Chemical Signatures ◽  
Chemical Determination ◽  
Materials Used ◽  
High Level ◽  
Beer Production ◽  
First Time ◽  
Detailed Chemical

Abstract Previous studies have shown that the Ancient Egyptians used malted wheat and barley as the main ingredients in beer brewing, but the chemical determination of the exact recipe is still lacking. To investigate the constituents of ancient beer, we conducted a detailed IR and GC-MS based metabolite analyses targeting volatile and non-volatile metabolites on the residues recovered from the interior of vats in what is currently the world’s oldest (c. 3600 BCE) installation for large-scale beer production located at the major pre-pharaonic political center at Hierakonpolis, Egypt. In addition to distinguishing the chemical signatures of various flavoring agents, such as dates, a significant result of our analysis is the finding, for the first time, of phosphoric acid in high level probably used as a preservative much like in modern beverages. This suggests that the early brewers had acquired the knowledge needed to efficiently produce and preserve large quantities of beer. This study provides the most detailed chemical profile of an ancient beer using modern spectrometric techniques and providing evidence for the likely starting materials used in beer brewing.

Sign in / Sign up

Export Citation Format

Share Document