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.

Genetic mutations in the TMEM53 gene have been linked to Craniotubular Dysplasia, Ikegawa Type (CTDI). To elucidate the etiology in a consanguineous family exhibiting the typical clinical phenotype of CTDI, trio whole exome sequencing (Trio-WES) was conducted, and a homozygous missense variant in the TMEM53 gene (NM_024587.4: c.634G > A: p.E212K) was identified. Both cellular experiments and patient blood sample analyses demonstrated that the p.E212K variant leads to the complete absence of TMEM53 protein. Further studies on ubiquitination confirmed that this variant introduced a novel ubiquitination site, causing protein degradation through the ubiquitin-proteasome system (UPS), resulting in TMEM53 protein deficiency. To our knowledge, this is the inaugural report of a missense variant creating a novel post-translational ubiquitination site that causes a Mendelian disease. This finding underscores the critical role of examining changes in post-translational modifications (PTMs) in determining the pathogenicity of gene variants.

» Wearable technologies (wearables), including smartphones, smartwatches, and sensors, such as accelerometers and inertial measurement units, enable continuous, real-time, and objective data collection on physical function, health behaviors, and patient perceptions.» Wearables can track mobility metrics such as step count, activity duration, and joint range of motion, providing valuable longitudinal insights into recovery trajectories.» In orthopaedic surgery, wearables support timely, personalized patient education and improve communication between patients and surgical teams, contributing to better functional outcomes and patient satisfaction.» Smart implants and virtual/augmented reality systems are emerging as innovative approaches to enhancing engagement and adherence during postoperative rehabilitation.» Key challenges to implementation include concerns about data privacy, accessibility, and integration into clinical workflows.