Astrocyte-mediated higher-order control of synaptic plasticity

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Abstract
The dynamics of higher-order topological signals are increasingly recognized as a key aspect of the activity of complex systems. A paradigmatic example are synaptic dynamics: synaptic efficacy changes over time driven by different mechanisms. Beyond traditional node-driven short-term plasticity, the role of astrocyte modulation through higher-order interactions, in the tripartite synapse, is increasingly recognized. However, the competition and interplay between node-driven and higher-order mechanisms remain poorly understood. Here, we introduce a higher-order model of the tripartite synapse, accounting for astrocyte-synapse-neuron interactions in short-term plasticity, such that astrocyte gliotransmission and pre-synaptic facilitation jointly modulate neurotransmitter release, generalizing earlier short-term plasticity models. We study these mechanisms in a minimal recurrent motif—a directed ring of three excitatory neurons—where one neuron receives external stimulation. Due to strong recurrence, the circuit is prone to self-sustained activity, often ignoring external input. By introducing higher-order interactions via astrocyte modulation, we show this robustly stabilizes circuit dynamics and expands the parameter space supporting stimulus-driven activity. Our findings highlight how astrocytes reshape effective connectivity through higher-order interactions—even in simple recurrent circuits.

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