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Latest Curated Articles

The curious case of dopaminergic prediction errors and learning associative information beyond value.

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Transient changes in the firing of midbrain dopamine neurons have been closely tied to the unidimensional value-based prediction error contained in temporal difference reinforcement learning models. However, whereas an abundance of work has now shown how well dopamine responses conform to the predictions of this hypothesis, far fewer studies have challenged its implicit assumption that dopamine is not involved in learning value-neutral features of reward. Here, we review studies in rats and humans that put this assumption to the test, and which suggest that dopamine transients provide a much richer signal that incorporates information that goes beyond integrated value.

Are oligodendrocytes bystanders or drivers of Parkinson's disease pathology?

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The major pathological feature of Parkinson 's disease (PD), the second most common neurodegenerative disease and most common movement disorder, is the predominant degeneration of dopaminergic neurons in the substantia nigra, a part of the midbrain. Despite decades of research, the molecular mechanisms of the origin of the disease remain unknown. While the disease was initially viewed as a purely neuronal disorder, results from single-cell transcriptomics have suggested that oligodendrocytes may play an important role in the early stages of Parkinson's. Although these findings are of high relevance, particularly to the search for effective disease-modifying therapies, the actual functional role of oligodendrocytes in Parkinson's disease remains highly speculative and requires a concerted scientific effort to be better understood. This Unsolved Mystery discusses the limited understanding of oligodendrocytes in PD, highlighting unresolved questions regarding functional changes in oligodendroglia, the role of myelin in nigral dopaminergic neurons, the impact of the toxic environment, and the aggregation of alpha-synuclein within oligodendrocytes.

Dissociable roles of central striatum and anterior lateral motor area in initiating and sustaining naturalistic behavior.

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Understanding how corticostriatal circuits mediate behavioral selection and initiation in a naturalistic setting is critical to understanding behavior choice and execution in unconstrained situations. The central striatum (CS) is well poised to play an important role in these spontaneous processes. Using fiber photometry and optogenetics, we identify a role for CS in grooming initiation. However, CS-evoked movements resemble short grooming fragments, suggesting additional input is required to appropriately sustain behavior once initiated. Consistent with this idea, the anterior lateral motor area (ALM) demonstrates a slow ramp in activity that peaks at grooming termination, supporting a potential role for ALM in encoding grooming bout length. Furthermore, optogenetic stimulation of ALM-CS terminals generates sustained grooming responses. Finally, dual-region photometry indicates that CS activation precedes ALM during grooming. Taken together, these data support a model in which CS is involved in grooming initiation, while ALM may encode grooming bout length.
Latest Updated Curations

Basal Ganglia Advances

 
 
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Progress in Voltage Imaging

 
 
Recent advances in the field of Voltage Imaging, with a special focus on new constructs and novel implementations.

Navigation & Localization

 
 
Work related to place tuning, spatial navigation, orientation and direction. Mainly includes articles on connectivity in the hippocampus, retrosplenial cortex, and related areas.
Most Popular Recent Articles

Index.

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Pleiotropic Effects of Red and Purple Pericarp Genes on Seed Coating Patterns, Flavonoids, Dormancy and Germination in Rice.

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Seeds are coated with pigments presumably to promote plant adaptation. To understand the adaptive mechanisms of seed pigment traits, allelic variants of the red (Rc/rc) and purple (Pb/pb) pericarp color genes were assembled into the same genetic background to identify the trait development patterns and pleiotropies of the loci on seed flavonoids, dormancy and germination in rice (Oryza sativa). Non-allelic recombination and epistasis of the loci dictated four patterns of the trait development from 5 to 40 days post anthesis (DPA). The Rc- and Pb-controlled pigments were synthesized in the same lower epidermal cells but compartmented in the cells and lignified wall area, respectively, after 10 d. Four flavan-3-ols (catechin, epicatechin and their dimeric procyanidins) and anthocyanins (AC) were detected in the Pb and Rc systems, respectively, with catechin being most abundant. Both genes affected seed primary dormancy, and imbibition and germination velocities of the dormancy-released seeds. Additive effects of the loci contributed most to the variances for all the pleiotropic traits, the development time and its interaction with the additive components influenced the flavonoid contents, and the additive-by-additive epistasis modified the AC content and dormancy level. Thus, seed pigment traits influence plant adaptation likely through a series of pleiotropies, including the coat structure, enhanced dormancy, and reduced germination speed. The differences between the Rc and Pb loci in the flavonoid type/content and the size of pleiotropic effects could partly explain the predominance of red pericarp-colored genotypes in wild and weedy rice and in pigmented specialty cultivars.

Hantaan virus-derived peptides that stabilize HLA-E could abrogate inhibition of CD56dimNKG2A+ NK cells.

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NK cells could participate in the pathogenesis process of virus infectious diseases through the inhibitory receptor CD94/NKG2A interacting with HLA-E/virus-derived peptide complex. However, the effects and mechanisms of NKG2A-HLA-E axis-mediated NK cell responses in hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus (HTNV) infection remain unclear. Single-cell RNA sequencing and flow cytometry were employed to analyze the phenotype and function of different NK cell subsets in HFRS patients. The K562/HLA-E cells binding assay was used for peptide affinity detection. The binding capacity of HLA-E/peptide-CD94/NKG2A was detected using ligand-receptor binding assay and tetramer staining. The cytotoxicity assay of NK cells against peptide-pulsed K562/HLA-E cells was conducted for functional evaluation. In this study, CD56dimCD16+NKG2A+ NK cells were the main subset in HFRS patients, showing activation and proliferation phenotypes with NKG2C-CD57- and the ability to secrete tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and cytotoxic mediators. Notably, none of the four identified HTNV epitopes presented by HLA-E could be recognized by CD94/NKG2A on CD56dimNKG2A+ NK cells. Furthermore, the subset of CD56dimNKG2A+ NK cells showed the enhanced cytolytic capacity against HTNV peptide pulsed K562/HLA-E cells ex vivo. Taken together, the findings demonstrate that HTNV-derived peptides presented by HLA-E could "abrogate" the inhibition of CD56dimNKG2A+ NK cells, contributing to the antiviral immune response in HFRS patients.
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