Becker, SophiaNold, AndreasTchumatchenko, Tatjana2023-02-272023-02-272023-02-272022-10-0110.1371/journal.pcbi.1010543https://infoscience.epfl.ch/handle/20.500.14299/195242WOS:000925007200015Short-term synaptic plasticity and modulations of the presynaptic vesicle release rate are key components of many working memory models. At the same time, an increasing number of studies suggests a potential role of astrocytes in modulating higher cognitive function such as WM through their influence on synaptic transmission. Which influence astrocytic signaling could have on the stability and duration of WM representations, however, is still unclear. Here, we introduce a slow, activity-dependent astrocytic regulation of the presynaptic release probability in a synaptic attractor model of WM. We compare and analyze simulations of a simple WM protocol in firing rate and spiking networks with and without astrocytic regulation, and underpin our observations with analyses of the phase space dynamics in the rate network. We find that the duration and stability of working memory representations are altered by astrocytic signaling and by noise. We show that astrocytic signaling modulates the mean duration of WM representations. Moreover, if the astrocytic regulation is strong, a slow presynaptic timescale introduces a 'window of vulnerability', during which WM representations are easily disruptable by noise before being stabilized. We identify two mechanisms through which noise from different sources in the network can either stabilize or destabilize WM representations. Our findings suggest that (i) astrocytic regulation can act as a crucial determinant for the duration of WM representations in synaptic attractor models of WM, and (ii) that astrocytic signaling could facilitate different mechanisms for volitional top-down control of WM representations and their duration.Author summaryThe ability to form memories and recall them is one of the fascinating features of our brain. Working memory operates like a memory scratch pad storing ongoing information for further processing. Here, we present a computational model dissecting the influence of astrocytes on the stability and duration of working memories. We find that a long astrocytic time constant can influence the mean duration of working memory representations and generate a "window of vulnerability", during which some memories are tagged for long-term survival while some are terminated. The fraction of memories in the survival and termination groups could be regulated by adjusting the strength of astrocytic feedback or its time constant. This indicates that astrocytic signaling can be viewed as a candidate mechanism for top-down control of working memory representations and their duration.Biochemical Research MethodsMathematical & Computational BiologyBiochemistry & Molecular Biologytext::journal::journal article::research article