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Ou, Z.-Y. A.

Publications and source records attributed to Ou, Z.-Y. A..

2 recordsLinked to original sources

Selective attention is insensitive to reward and to dopamine in Parkinson's disease

Patients with Parkinsons disease exhibit reduced reward sensitivity in addition to early cognitive deficits, among which attention impairments are common. Attention allocation is controlled at multiple levels and recent work has shown that reward, in addition to its role in the top-down goal-directed control of attention, also guides the automatic allocation of attention resources, a process thought to rely on striatal dopamine. Whether Parkinsons patients, due to their striatal dopamine loss, suffer from an inability to use reward information to guide the allocation of their attention is unknown. To address this question, we tested Parkinsons patients (n=43) ON and OFF their dopaminergic medication, and compared them to a group of older controls (n=31). We used a standard two-phase attention capture task in which subjects were first implicitly trained to make colour-reward associations. In the second phase, the previously reward-associated colours were used as distractors in a visual search task. We found that patients did not use reward information to modulate their attention; they were similarly distracted by the presence of low and high-reward distractors. However, contrary to our predictions, we did not find evidence that dopamine modulated this inability to use reward to guide attention allocation. Additionally, we found slightly increased overall distractibility in Parkinsons patients compared to older controls, but interestingly, the degree of distractibility was not influenced by dopamine replacement. Our results suggest that loss of reward-guided attention allocation may contribute to early attention deficits and raise the possibility that this inability to prioritize cognitive resource allocation could contribute to executive deficits more broadly in Parkinsons disease.

neuroscience↗

Lysosome enlargement during inhibition of the lipid kinase PIKfyve proceeds through lysosome coalescence

Lysosomes receive and degrade cargo from endocytosis, phagocytosis and autophagy. They also play an important role in sensing and instructing cells on their metabolic state. The lipid kinase PIKfyve generates phosphatidylinositol-3,5-bisphosphate to modulate lysosome function. PIKfyve inhibition leads to impaired degradative capacity, ion dysregulation, abated autophagic flux, and a massive enlargement of lysosomes. Collectively, this leads to various physiological defects including embryonic lethality, neurodegeneration and overt inflammation. While being the most dramatic phenotype, the reasons for lysosome enlargement remain unclear. Here, we examined whether biosynthesis and/or fusion-fission dynamics contribute to swelling. First, we show that PIKfyve inhibition activates TFEB, TFE3 and MITF enhancing lysosome gene expression. However, this did not augment lysosomal protein levels during acute PIKfyve inhibition and deletion of TFEB and/or related proteins did not impair lysosome swelling. Instead, PIKfyve inhibition led to fewer but enlarged lysosomes, suggesting that an imbalance favouring lysosome fusion over fission causes lysosome enlargement. Indeed, conditions that abated fusion curtailed lysosome swelling in PIKfyve-inhibited cells.\n\nSummary statementPIKfyve inhibition causes lysosomes to coalesce, resulting in fewer, enlarged lysosomes. We also show that TFEB-mediated lysosome biosynthesis does not contribute to swelling.

cell biology↗