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.

Despite advances in cancer research, treating malignancies remains challenging due to issues like drug resistance, disease heterogeneity, and the limited efficacy of current therapies, particularly in relapsed or refractory cases. In recent years, several drugs originally approved for non-cancer indications have shown potential in cancer treatment, demonstrating anti-proliferative, anti-metastatic, and immunomodulatory effects. Drug repurposing has shown immense promise due to well-established safety profiles and mechanisms of action of the compounds. However, the implementation is fraught with clinical, logistical, regulatory, and ethical challenges, especially in diseases such as leukaemia and multiple myeloma. This chapter examines the treatment challenges in leukaemia and multiple myeloma, focusing on the role of drug repurposing in addressing therapeutic resistance and disease variability. It highlights the potential of personalized, tailored combination therapies, using repurposed drug components, to offer more effective, targeted, and cost-efficient treatment strategies, overcoming resistance and improving patient outcomes.

Upon inflammation, the bone marrow (BM) landscape undergoes significant architectural and functional modifications. Stimulation of the hematopoietic niche triggers a series of lightning events, which begin with stem/progenitor blood elements mobilization and culminates with the activation of immune responses. Ageing partially mirrors this process, albeit with a propensity towards chronic inflammation and immune dysfunction. Age-related chronic inflammation disrupts bone homeostasis and accompanies impaired tissue regeneration. Thus, focusing on the bone marrow's dynamics during inflammatory bone diseases could lay the way for the development of novel therapeutic platforms aimed at niche reprogramming. Herein, we summarize inflammatory and age-induced processes in multiple BM compartments, with particular reference to hematopoietic, stromal stem/progenitor cells, and mature immunocytes. Finally, we focus on autophagy and its potential to clinically re-modulate the pathological "flogistic" bias, possibly by restoring functional phenotypes within the bone marrow niche elements.