Figure 1.

Interaction between Ca²⁺ and glial transmitters. G-protein-coupled receptors activated by glutamate, GABA, and ATP can increase [Ca²⁺]_i in astrocytes through the PLC/IP3 signal cascade. The increase of [Ca²⁺]_i can in turn enhance the release of glial transmitters such as glutamate, GABA, ATP or D-ser by astrocytes and influence the excitability, synaptic plasticity, and synaptic electrophysiology of postsynaptic neurons. Among them, glutamate induces an NMDAR-mediated inward membrane current in neurons to regulate synaptic excitability and synchronize its action potential. ATP mainly activates the P2y1 receptor from the P2 receptor family, which increases [Ca2+]i, and the release of D-ser also plays a similar role by binding with NMDAR. And astrocytes increase the transmission efficiency of CA1 pyramidal cells by activating the subtype 5 metabotropic glutamate receptor (mGluR5) and presynaptic adenosine A2A receptor, resulting in the upregulation of synaptic transmission and induction of LTP At the same time, D-ser controls the activation of NMDA receptors when glutamate is released from synapses.