Glia: they make your memories stick!

Synaptic plasticity underlies higher brain functions such as learning and memory. At glutamatergic synapses in the vertebrate central nervous system, plasticity usually requires changes in the number of postsynaptic AMPA receptors. Recently, several studies have revealed that glial cells play an important role in regulating postsynaptic AMPA receptor density. This is accomplished through the release of gliotransmitters such as d-serine, ATP and TNF-α. More specifically, the availability of d-serine, the endogenous co-agonist of N-methyl-d-aspartate receptors in many brain areas, governs the induction of long-term potentiation and long-term depression. Meanwhile, ATP and TNF-α trigger long-lasting increases in synaptic strength at glutamatergic hypothalamic and hippocampal inputs, respectively, through mechanisms that promote AMPA receptor insertion in the absence of coincident presynaptic and postsynaptic activity. These data clearly demonstrate a vital role for glia in plasticity and argue that their contributions to brain function extend well beyond their outdated role as cellular ‘glue’.