Targeted Neuronal Stimulation Modulates Working Memory via Astrocytic Interactions: Insights from a Spiking Neuron-Astrocyte Model

Brain stimulation is a promising approach to cognitive enhancement, particularly for improving working memory (WM) function. However, conventional stimulation paradigms often overlook the active contributions of astrocytes and treat stimulation as an all-or-none intervention without considering spatial information or studying the competition among temporal dynamics. In this study, we employ a spiking neuron-astrocyte network model comprising excitatory neurons, inhibitory neurons, astrocytes, and integrated recording and stimulation electrodes within a 2D structure. This framework allows us to investigate how targeted neuronal stimulation modulates WM via neuroglial interactions. We demonstrate that WM emerges from a hierarchy of temporal dynamics: rapid neuronal spiking, intermediate synaptic glutamate release, and slow astrocytic calcium signaling. Through targeted neuronal stimulation across three experiments, we demonstrate that: (1) Excitatory stimulation enhances WM in synaptically impaired networks by restoring both astrocytic calcium dynamics and neuronal activity through boosting the functionality of abnormal synapses. (2) Inhibitory stimulation in healthy networks suppresses excitatory neuronal firing, blocks the neuroglial feedback loop necessary for WM maintenance, and shows how transient inhibition morphs into lasting dysfunction. Interestingly, we found that delayed reaction of dynamics can serve as a defense mechanism against such disruptions, highlighting the protective role of the temporal buffer in neuroglial networks. (3) Excitatory stimulation during training augments the encoding process by elevating astrocytic calcium levels associated with novel input patterns, thereby improving WM performance. To our knowledge, this study is the first to examine WM manipulation through neuronal stimulation while posing astrocytes as key mediators. Our findings underscore the necessity for spatiotemporal precision in neuronal stimulation protocols that leverage competing neuroglial temporal dynamics for cognitive enhancement, therapeutic interventions, and bioinspired systems.