Slow AMPA receptors in hippocampal principal cells

Summary Glutamate receptor ion channels such as the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor mediate the majority of fast excitatory neurotransmission in the vertebrate CNS. AMPA receptors canonically provide the fast, millisecond component of the synaptic current. However, we found that about two-thirds of principal cells in the mouse hippocampus express AMPA receptors that do not desensitize and stay active for up to half a second. These receptors are expressed at synapses with a sparse but flat spatial distribution. The resulting increase in charge transfer allows single connections to reliably trigger action potentials. Biophysical and pharmacological observations imply that slow AMPA receptors incorporate γ-8 and other auxiliary proteins, and their activation lengthens individual miniature synaptic currents. Synaptic connections harboring slow AMPARs should have unique roles in hippocampal function.