Computational Modeling of Hyperpolarizing Astrocytic Influence on Cortical Up-Down State Transitions

Abstract

The Up-Down dynamics seen in cortical structures during non-rapid-eye-movement (NREM) sleep, anesthetized states, and quiet wakefulness is the spontaneous alternation between phases of heightened firing activity (referred to as the Up state) and periods of neuronal inactivity (termed the Down state) within neural networks. By leveraging bistable dynamics imposed by a depolarising astrocyte population, in the current paper, we introduced a hyperpolarising astrocyte population to an existing model of Up-Down dynamics to account for biological relevance. We created a computational rate model that includes populations of depolarizing and hyperpolarizing astrocytes and neurons. To optimize model parameters, we used the Elementary Effects (EE) test. It was followed by linear stability analysis to locate bistable regimes in the parameter hyperspace. The addition of hyperpolarizing gliotransmission perturbed model dynamics, indicating its sensitivity to qualitatively differing architectures. We then identified a bistable regime within the dynamics spectrum. According to the EE test, the strength of cell population coupling is a low-sensitivity parameter, possibly due to neuroplastic changes. We also found that the threshold of excitatory cell populations and the strength of adaptation are high-sensitivity parameters, whereas the threshold of inhibitory cell populations is low-sensitivity. Our model enables the possibility of testing biologically relevant theories of hyperpolarizing gliotransmission, where data remains scant.