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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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.
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.