Unique functions of kainate receptors in the brain are determined by the auxiliary subunit Neto1

Ionotropic glutamate receptors principally mediate fast excitatory transmission in the brain. Among the three classes of ionotropic glutamate receptors, kainate receptors (KARs) display a categorical brain distribution, which has been historically defined by (3)H-radiolabeled kainate binding. Compared with recombinant KARs expressed in heterologous cells, synaptic KARs exhibit characteristically slow rise-time and decay kinetics. However, the mechanisms responsible for these unique KAR properties remain unclear. Here we found that both the distinct high affinity biding pattern in the mouse brain and the channel properties of native KARs are determined by the KAR auxiliary subunit Neto1. Through modulation of agonist binding affinity and off-kinetics of KARs, but not trafficking of KARs, Neto1 determines both KAR high affinity binding pattern and the distinctively slow kinetics of postsynaptic KARs. By regulating KAR-EPSC kinetics, Neto1 can control synaptic temporal summation, spike generation and fidelity.