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.

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.

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.

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

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

The NHS Clinical Entrepreneur Programme (CEP) was established to promote leadership and innovation within the UK health-care system, though its implementation raises important questions about resource allocation and alignment with NHS founding principles. This study aims to systematically review the literature on the CEP and provide a critical reflective analysis of its impact, considering both its potential benefits and tensions with frontline service delivery in an already strained NHS.

Millions of people worldwide are chronically exposed to environmental arsenic through drinking water, increasing their risk of various adverse cardiometabolic outcomes. To understand the inter-individual variation in arsenic susceptibility, this systematic review explores all epidemiological evidence on interactions between single nucleotide polymorphisms (SNPs) and arsenic exposure in relation to cardiometabolic health. Five electronic databases were searched until April 2023. From 42,202 retrieved publications, 18 candidate gene-environment (cGxE) studies were included, and no genome-wide association studies were found. Of 676 SNPs in 148 genes tested, 40 SNPs in 24 genes, 4 haplotypes and combined SNPs in , were reported to statistically significantly interact with arsenic exposure. These genes were involved in arsenic metabolism oxidative stress or defence, DNA damage repair, endothelial (dys) function, inflammation or immune function, tumour suppressor activity, or were previously implicated in cardiometabolic disease pathways. Most studies did not explore the same SNPs (or strong proxies), and none of the identified SNP-arsenic interactions were replicated for the same arsenic species and cardiometabolic outcome. Whilst some SNPs are suggestive of influencing susceptibility to arsenic for various cardiometabolic outcomes, further research is needed to understand the interplay between arsenic and genetic variants, identify at-risk populations, and improve risk assessment.