Synaptic Drive at Developing Synapses: Transient Upregulation of Kainate Receptors

At the onset of a period of intense synaptic refinement initiated by synchronized eye opening (EO), rapid changes in postsynaptic NMDA receptor and AMPA receptor currents (NMDARcs and AMPARcs) occur within the superficial visual layers of the rodent superior colliculus (sSC; Lu and Constantine-Paton [2004]: Neuron 43:237–249). Subsequently, evoked non-NMDARc amplitudes increase, but by 2 weeks after EO (AEO) they decrease significantly. Here, using whole-cell patch-clamp recording, we demonstrate that small, slowly desensitizing excitatory kainate receptor currents (KARcs) are responsible for the rise and subsequent fall in non-NMDARcs. The increase in KAR transmission parallels inhibitory GABAA responses that plateau at 7 days AEO. By 2 weeks AEO, KARcs are gone. AMPARcs remain unchanged during the appearance and disappearance of the KARcs, despite increases in sSC neuropil activity and continued refinement of inputs to individual sSC neurons. We suggest that in the interval of heightened activity, before SC inhibition matures, many AMPARcs desensitize and are relatively ineffective at relieving the Mg2+ block on NMDARs. This transient appearance of slowly desensitizing, long-duration KARcs may provide increased membrane depolarization necessary for NMDAR function and continuation of synaptic refinement. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 737–750, 2010National Institutes of Health (U.S.) (Grant EY01407)Amyotrophic Lateral Sclerosis Association (Pierre L.de Bourgknecht ALS Research Foundation