Biology subjects

Mesquita, A.

Publications and source records attributed to Mesquita, A..

3 recordsLinked to original sources

bioRxiv2021

Lamp1 mediates lipid transport, but is dispensable for autophagy in Drosophila

The endolysosomal system not only is an integral part of the cellular catabolic machinery that processes and recycles nutrients for synthesis of biomaterials, but also acts as signaling hub to sense and coordinate the energy state of cells with growth and differentiation. Lysosomal dysfunction adversely influences vesicular transport-dependent macromolecular degradation and thus causes serious problems for human health. In mammalian cells, loss of the lysosome associated membrane proteins LAMP1/2 strongly impacts autophagy and cholesterol trafficking. Here we show that the previously uncharacterized Drosophila Lamp1 is a bona fide homolog of vertebrate LAMP1/2. Surprisingly and in contrast to Lamp1/2 double mutant mice, Drosophila Lamp1 is not required for viability or autophagy, suggesting that autophagy defects in Lamp1/2 mutants may have indirect causes. However, Lamp1 deficiency results in an expansion of the acidic compartment in flies. Furthermore, we find that Lamp1 mutant larvae have defects in lipid metabolism as they show elevated levels of sterols and diacylglycerols (DAGs). Since DAGs are the main lipid species used for transport though the hemolymph (blood) in insects, our results indicate broader functions of Lamp1 in lipid transport. Our findings make Drosophila an ideal model to study the role of LAMP proteins in lipid assimilation without the confounding effects of their storage and without interfering with autophagic processes.

cell biology↗

bioRxiv2021

Acute stress blunts prediction error signals in the dorsal striatum during reinforcement learning

Reinforcement learning, which implicates learning from the rewarding and punishing outcomes of our choices, is critical for adjusted behaviour. Acute stress seems to affect this ability but the neural mechanisms by which it disrupts this type of learning are still poorly understood. Here, we investigate whether and how acute stress blunts neural signalling of prediction errors during reinforcement learning using model-based functional magnetic resonance imaging. Male participants completed a well-established reinforcement learning task involving monetary gains and losses whilst under stress and control conditions. Acute stress impaired participants' behavioural performance towards obtaining monetary gains, but not towards avoiding losses. Importantly, acute stress blunted signalling of prediction errors during gain and loss trials in the dorsal striatum -- with subsidiary analyses suggesting that acute stress preferentially blunted signalling of positive prediction errors. Our results thus reveal a neurocomputational mechanism by which acute stress may impair reward learning.

neuroscience↗

bioRxiv2020

Acute stress impairs reward learning in men

Acute stress is ubiquitous in everyday life, but the extent to which acute stress affects how people learn from the outcomes of their choices is still poorly understood. Here, we investigate how acute stress impacts reward and punishment learning in men using a reinforcement-learning task. Sixty-two male participants performed the task whilst under stress and control conditions. We observed that acute stress impaired participants choice performance towards monetary gains, but not losses. To unravel the mechanism(s) underlying such impairment, we fitted a reinforcement-learning model to participants trial-by-trial choices. Computational modeling indicated that under acute stress participants learned more slowly from positive prediction errors -- when the outcomes were better than expected -- consistent with stress-induced dopamine disruptions. Such mechanistic understanding of how acute stress impairs reward learning is particularly important given the pervasiveness of stress in our daily life and the impact that stress can have on our wellbeing and mental health.

neuroscience↗