Biology subjects

Wilhelm, S.

Publications and source records attributed to Wilhelm, S..

3 recordsLinked to original sources

bioRxiv2024

Featural and spatial interference with functionally active and passive items in working memory

Functionally active and passive states in working memory have been related to different neural mechanisms. Memoranda in active states might be maintained by persistent neural firing, whereas memoranda in passive states might be maintained through short-term synaptic plasticity. We reasoned that this might make these items differentially susceptible to interference during maintenance, in particular that passively maintained items might be more robust. To test this hypothesis, we gave our participants a working memory task in which one item was prioritised (active) by always probing it first, while the other item was deprioritised (passive) by always probing it second. In two experiments, on half the trials, we presented an interfering task during memory maintenance, in which the stimuli matched either the feature dimension of the memory items (colour or orientation), or their spatial location. Whether the interfering task appeared on a given trial was unpredictable. In a third experiment where participants were given prior knowledge of the interference condition, and finally in a fourth experiment we used a reward-based prioritisation cue. Across experiments, we found that both active and passive memory items were affected by interference to a similar extent, with overall performance being closely matched in all experiments. We further investigated precision and probability of target response parameters from the standard mixture model, which also showed no differences between states. We conclude that active and passive items, although potentially stored in different neuronal states, do not show differential susceptibility to interference. Public significance statementThe ability to briefly remember information is critical to human cognition. Our so-called working memory is nevertheless rather limited, able to hold only a few items at any one time, and prone to forgetting when we are briefly distracted. Yet, there is reason to believe that not all information in working memory is equally vulnerable. Items that are more passively stored, because they will only be required after some time, might be more resilient to interference. Items that are stored actively, for more immediate recall, might be more easily disrupted. Here, we investigated the effect of an interference task on the retention of both active and passive items in working memory. Our results showed that active and passive items are equally affected by interference, suggesting that resilience in working memory does not depend on the functional state of the items therein.

neuroscience↗

bioRxiv2023

Spatially and Functionally Distinct mTORC1 Entities Orchestrate the Cellular Response to Amino Acid Availability

Amino acid (AA) availability is a robust determinant of cell growth, through controlling mTORC1 activity 1. According to the predominant model in the field, AA sufficiency drives the recruitment and activation of mTORC1 on the lysosomal surface by the heterodimeric Rag GTPases, from where it coordinates the majority of cellular processes (reviewed in 2,3). Importantly, however, 15 years after its initial discovery, the teleonomy of the proposed lysosomal regulation of mTORC1, and where mTORC1 acts on its effector proteins remain enigmatic 4. Here, by using multiple pharmacological and genetic means to perturb the lysosomal AA sensing and protein recycling machineries, we describe the spatial separation of mTORC1 regulation and downstream functions in mammalian cells, with lysosomal and non-lysosomal mTORC1 phosphorylating distinct substrates in response to different AA sources. Moreover, we reveal that a fraction of mTOR localizes at lysosomes due to basal lysosomal proteolysis that locally supplies new AAs, even in cells grown in the presence of extracellular nutrients, whereas cytoplasmic mTORC1 is regulated by exogenous AAs. Overall, our study substantially expands our knowledge about the topology of mTORC1 regulation by AAs, and hints at the existence of distinct, Rag- and lysosome-independent mechanisms that control its activity at other subcellular locations. Given the importance of mTORC1 signalling and AA sensing for human ageing and disease 2, our findings will likely open new directions toward the identification of function-specific mTORC1 regulators, and suggest new targets for drug discovery against conditions with dysregulated mTORC1 activity in the future.

cell biology↗

bioRxiv2023

Maintenance of colour memoranda in activity-quiescent working memory states: Evidence from impulse perturbation

The neural mechanisms underlying working memory maintenance pose a challenge for investigation, as sustained neural activity may not always be observable. To address this, the method of impulse perturbation has been employed to examine memorized information during activity-quiescent periods. However, this approach has mainly focused on spatially localized or referenced stimuli, leaving it unclear whether non-spatial memoranda share similar neural maintenance mechanisms. This study aimed to fill this gap by applying the impulse perturbation method to working memory for colours, which are inherently non-spatial stimuli. EEG data from 30 participants performing a delayed match-to-sample task were analysed, with one of the presented items being retro-cued as task-relevant. Our findings indicate that both cued and uncued colours could be decoded from impulse-evoked activity, in contrast to previous reports on working memory for orientation gratings. Additionally, we explored colour decoding from ongoing oscillations in the alpha band and discovered that cued items could be decoded, potentially influenced by attention, whereas uncued items could not. These results suggest subtle differences between the representation of colours and stimuli with spatial properties. However, they also demonstrate that both types of information can be accessed through visual impulse perturbation, regardless of their specific neural states.

neuroscience↗