Targeted neuronal stimulation modulates working memory via astrocytic interactions: Insights from a spiking neuron-astrocyte model.

Brain stimulation offers promising avenues for cognitive enhancement, yet conventional paradigms often overlook the active role of astrocytes and treat stimulation as an all-or-none intervention without considering spatial information or competition among temporal dynamics. We present a spiking neuron-astrocyte network model integrated with 2D recording and stimulation arrays to investigate how targeted neuronal stimulation modulates working memory (WM) via neuroglial interactions. WM depends on a temporal hierarchy: rapid neuronal spiking, synaptic glutamate release, and slow astrocytic calcium signaling. In three experiments we demonstrate: (1) targeted excitatory stimulation restores WM in synaptically impaired networks by reactivating astrocytic calcium dynamics; (2) inhibitory stimulation disrupts WM maintenance by blocking the necessary neuroglial feedback loop; and (3) excitatory stimulation during the sample phase augments WM encoding for novel patterns. Our findings underscore the importance of spatiotemporal precision in stimulation protocols and establish astrocytes as pivotal mediators, providing a new framework for bio-inspired memory systems.