Astrocyte-mediated higher-order control of synaptic plasticity

Area of Science:

• Computational Neuroscience
• Systems Neuroscience
• Astrocyte Biology

Background:

• Synaptic plasticity, crucial for complex systems, involves dynamic efficacy changes.
• Traditional models focus on node-driven short-term plasticity.
• Astrocyte modulation via higher-order interactions in tripartite synapses is gaining recognition but remains poorly understood.

Purpose of the Study:

• To introduce a higher-order model of the tripartite synapse.
• To investigate the interplay between node-driven and higher-order mechanisms in short-term plasticity.
• To analyze how astrocyte modulation stabilizes circuit dynamics and influences stimulus-driven activity.

Main Methods:

• Developed a higher-order model of the tripartite synapse incorporating astrocyte-synapse-neuron interactions.
• Studied a minimal recurrent motif: a directed ring of three excitatory neurons with external stimulation.
• Analyzed circuit dynamics under astrocyte modulation using computational modeling.

Main Results:

• The higher-order model integrates astrocyte gliotransmission and pre-synaptic facilitation to modulate neurotransmitter release.
• Astrocyte modulation robustly stabilizes circuit dynamics, counteracting self-sustained activity.
• Higher-order interactions expand the parameter space supporting stimulus-driven activity, even in simple recurrent circuits.

Conclusions:

• Astrocytes reshape effective connectivity through higher-order interactions.
• Astrocyte modulation is critical for stabilizing neural circuit dynamics and maintaining stimulus responsiveness.
• The study provides a generalized framework for short-term plasticity incorporating glial influence.