Select mechanisms for astrocyte-modulated neuronal signaling.
Top: Simple model circuit showing three linearly connected neurons (n) and associated astrocytes (a). at two synaptic (S) connections. Synapse 1: Influx of calcium into gap junction-coupled astrocytes via TRPA1 channels occurs in response to local neuronal activity. Elevation of astrocytic calcium causes astrocyte activation and release of gliotransmitters including D-serine, which induces NMDAR-dependent LTP. Synapse 2: Elevation of astrocytic calcium can also drive release of the gliotransmitters ATP and glutamate, which can stimulate pre-synaptic adenosine and metabotrophic glutamate (mGluR) receptors, respectively, to promote signaling of downstream neurons and drive the flow of information through the circuit