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Kainate receptors mediate a slow postsynaptic current in hippocampal CA3 neurons

Abstract

Glutamate, the neurotransmitter at most excitatory synapses in the brain, activates a variety of receptor subtypes that can broadly be divided into ionotropic (ligand-gated ion channels) and metabotropic (G-protein-coupled) receptors. Ionotropic receptors mediate fast excitatory synaptic transmission, and based on pharmacological and molecular biological studies are divided into NMDA and non-NMDA subtypes. The non-NMDA receptor group is further divided into AMPA and kainate subtypes1. Virtually all fast excitatory postsynaptic currents studied so far in the central nervous system are mediated by the AMPA and NMDA subtypes of receptors. Surprisingly, despite extensive analysis of their structure, biophysical properties and anatomical distribution, a synaptic role for kainate receptors in the brain has not been found2. Here we report that repetitive activation of the hippocampal mossy fibre pathway, which is associated with high-affinity kainate binding3 and many of the kainate receptor subtypes4,5,6,7,8, generates a slow excitatory synaptic current with all of the properties expected of a kainate receptor. This activity-dependent synaptic current greatly augments the excitatory drive of CA3 pyramidal cells.

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Figure 1: Repetitive activation of mossy fibres but not associational/commissional fibres activates a GYKI 53655 resistant, CNQX-sensitive synaptic potential, as revealed by field-potential recording.
Figure 2: Characterization of the GYKI 53655 (GYKI)-resistant EPSC with whole-cell recording.
Figure 3: Characterization of responses to applied kainate.
Figure 4: Characterization of the responses to glutamate and the lack of effect of kainate on the frequency of miniature EPSCs.

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Acknowledgements

We thank D. Leander for GYKI 53655; M. Frerking, S. Oliet and K. Vogt for comments on the manuscript; and H. Czerwonka for secretarial assistance. R.A.N. is a member of the Keck Center for Integrative Neuroscience and the Silvio Conte Center for Neuroscience Research. R.C.M. is a member of the Center for Neurobiology and Psychiatry, and the Center for the Neurobiology of Addiction. R.A.N. and R.C.M. are supported by grants from the NIH.

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Correspondence to Roger A. Nicoll.

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Castillo, P., Malenka, R. & Nicoll, R. Kainate receptors mediate a slow postsynaptic current in hippocampal CA3 neurons. Nature 388, 182–186 (1997). https://doi.org/10.1038/40645

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