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The Journal of Neuroscience, September 7, 2005, 25(36):8229-8239; doi:10.1523/JNEUROSCI.1469-05.2005

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Neurobiology of Disease
Recurrent Mossy Fibers Establish Aberrant Kainate Receptor-Operated Synapses on Granule Cells from Epileptic Rats

Jérôme Epsztein, Alfonso Represa, Isabel Jorquera, Yehezkel Ben-Ari, and Valérie Crépel

Institut de Neurobiologie de la Méditerranée, Institut National de la Santé et de la Recherche Médicale, Unité 29, and Université de la Méditerranée, Parc Scientifique de Luminy, 13273 Marseille Cedex 09, France

Glutamatergic mossy fibers of the hippocampus sprout in temporal lobe epilepsy and establish aberrant synapses on granule cells from which they originate. There is currently no evidence for the activation of kainate receptors (KARs) at recurrent mossy fiber synapses in epileptic animals, despite their important role at control mossy fiber synapses. We report that KARs are involved in ongoing glutamatergic transmission in granule cells from chronic epileptic but not control animals. KARs provide a substantial component of glutamatergic activity, because they support half of the non-NMDA receptor-mediated excitatory drive in these cells. KAR-mediated EPSC_KAs are selectively generated by recurrent mossy fiber inputs and have a slower kinetics than EPSC_AMPA. Therefore, in addition to axonal rewiring, sprouting of mossy fibers induces a shift in the nature of glutamatergic transmission in granule cells that may contribute to the physiopathology of the dentate gyrus in epileptic animals.

Key words: kainate receptors; mossy fibers; granule cells; hippocampus; epilepsy; kainic acid

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Received April 14, 2005; revised July 14, 2005; accepted July 19, 2005.

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