Long-Term Depression of Synaptic Kainate Receptors Reduces Excitability by Relieving Inhibition of the Slow Afterhyperpolarization

Kainate receptors (KARs) are ionotropic glutamate receptors that also activate non-canonical G-protein-coupled signalling pathways to depress the slow afterhyperpolarization (sAHP). Here we show that long-term depression of KAR-mediated synaptic transmission (KAR LTD) at rat hippocampal mossy fiber synapses relieves inhibition of the sAHP by synaptic transmission. KAR LTD is induced by high frequency mossy fiber stimulation and natural spike patterns and requires activation of adenosine A(2A) receptors. Natural spike patterns also cause long-term potentiation of NMDA receptor-mediated synaptic transmission that overrides the effects of KAR LTD during low frequency synaptic input. However, KAR LTD is dominant at higher frequency synaptic stimulation where it decreases the cellular response by relieving inhibition of the sAHP. Thus we describe a form of glutamate receptor plasticity induced by natural spike patterns whose primary physiological function is to regulate cellular excitability