Synaptic strengthening through activation of Ca²⁺-permeable AMPA receptors

Postsynaptic Ca²⁺ elevation during synaptic transmission is an important trigger for short- and long-term changes in synaptic strength in the vertebrate central nervous system. The AMPA (α-amino-3-hydroxy-5- methyl-4-isoxazoleproprionate) receptors, a subfamily of glutamate receptors, mediate much of the excitatory synaptic transmission in the brain and spinal cord. It has been shown that a subtype of the AMPA receptor is Ca²⁺- permeable and is present in subpopulations of neurons. When synaptically localized, these receptors should mediate postsynaptic Ca²⁺ influx, providing a trigger for changes in synaptic strength. Here we show that Ca²⁺-permeable AMPA receptors are synaptically localized on a subpopulation of dorsal horn neurons, that they provide a synaptically gated route of Ca²⁺ entry, and that activation of these receptors strengthens synaptic transmission mediated by AMPA receptors. This pathway for postsynaptic Ca²⁺ influx may provide a new form of activity-dependent modulation of synaptic strength.