The curious case of dopaminergic prediction errors and learning associative information beyond value.
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?
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.
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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Progress in Voltage Imaging
Recent advances in the field of Voltage Imaging, with a special focus on new constructs and novel implementations.
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Work related to place tuning, spatial navigation, orientation and direction. Mainly includes articles on connectivity in the hippocampus, retrosplenial cortex, and related areas.
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Sometimes extracellular recordings fail for good reasons
Excitable cells are commonly studied via the extracellular potentials (EPs) they generate, which underlie signals in electroencephalography (EEG), electrocardiography (ECG), and multielectrode array (MEA) recordings. However, some excitable systems produce little or no detectable EPs, for reasons that remain poorly understood. Here we show mathematically that homogeneous excitable cells and tissues -- with spatially uniform ion channel distributions and no external stimulation -- are extracellularly silent even in the presence of full action potentials. Specifically, an isolated, autonomous cell with uniform membrane properties generates zero EP, independent of shape, kinetics, or model complexity. The result extends to coupled cells provided the tissue remains fully homogeneous. EPs emerge only from spatial inhomogeneities, propagating electrical waves, or applied currents. We demonstrate the physiological relevance of this principle in Purkinje neurons, where clustering of sodium channels enables ephaptic synchronization, while uniform cells remain asynchronous and undetectable extracellularly. We further show that connected human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and pancreatic {beta}-cells exhibit EPs in proportion to cellular or tissue-level heterogeneity. These findings offer a unifying explanation for the observed silence of some excitable cells and are consistent with experimental reports of strong intracellular signals accompanied by weak or absent EPs.
Integrated landscape genomics reveals biogeography and climate-driven local adaptation in high-altitudes
High-elevation environments harbor unique species adapted to altitudinal and environmental extremes. However, due to logistical challenges of sampling such species throughout their distribution across steep and varied terrains, studies often lack comprehensive evidence to understand patterns of population divergence, local adaptation, and how current adaptations may influence future vulnerability. In this study, we utilized the Tibetan Partridge (Perdix hodgsoniae), a high-altitude endemic bird found between 2800 and 5000 meters across the arid western and humid northeastern regions of the Sino-Himalayan landscape. This regions complex topography-characterized by tall mountains, deep valleys, and contrasting climatic conditions provided opportunities for investigating population divergence, local adaptation, and climate-related vulnerability. We integrated population-scale whole-genome sequencing with ecological, climatic, landscape, and morphological data to examine current patterns of local adaptation and forecast future risks. Our findings show that both biogeographic barriers and climatic variation drive rapid population divergence in P. hodgsoniae, reflected in distinct morphological traits and population genetic structure. Western populations, inhabiting dry and fragmented landscapes, exhibit adaptations to temperature extremes with low genetic diversity, reduced habitat suitability, limited gene flow, and weak connectivity, factors that increase their vulnerability to future environmental changes. In contrast, northeastern populations, living in more humid regions, show genetic adaptations linked to precipitation, maintain high genetic diversity and habitat connectivity, and may serve as evolutionary refugia under future climate scenarios. This study underscores the value of integrating genomic, ecological, and landscape data to reveal mechanisms of divergence and adaptation and to develop robust predictions for conservation planning under rapidly changing environmental conditions.