(A) Schematic diagram of synaptic interactions occurring between neuronal dendrites and separate axonal boutons, from neighbouring neurons, forming the excitatory synapse. Here, astrocytes can project their processes into the synaptic cleft where they can influence synaptic signalling. (Ai) Synaptic release of glutamate activates receptors (of which many are expected to be involved, depending on the brain region) and glutamate transporters on the astrocyte membrane. Glutamate (Glu) entering via glutamate transporters can either be actively converted into glutamine (Gln), lactate or glucose (to be stored as glycogen) or be used to generate ATP production via mitochondrial oxidation. Na⁺ influx occurs alongside glutamate entry and this rise can induce the reverse mode of the NCX, resulting in Ca²⁺ influx. This is another possible route for astrocyte Ca²⁺ entry (the other being activation of receptors), which can consequently be taken up by the mitochondrial uniporter and re-released in exchange for Na⁺. Ca²⁺ release by mitochondria can then induce the exocytotic release of glutamate. The Na⁺/K⁺-ATPase is important for ionic homoeostasis during astrocyte depolarization by actively extruding Na⁺ that accumulates with glutamate uptake. These actions reveal the intricate and crucial regulatory role provided by astrocytes at the excitatory synapse and the importance of mitochondrial ATP provision and Ca²⁺ buffering within their processes.