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Rôle des récepteurs kainate dans la transmission synaptique :
une étude dans l'hippocampe de rat contrôle et dans un modèle animal
d'épilepsie du lobe temporal

Abstract : Glutamate, the main excitatory neurotransmitter in the brain, acts on three main types of ionotropic receptors: AMPA (AMPARs), NMDA (NMDARs) and kainate (KARs) receptors. Classically, the activation of AMPARs is considered to be responsible for most of the excitatory drive on central neurons. However, recent studies suggest that KARs could also participate to excitatory synaptic transmission when large amount of glutamate are released (after repetitive and/or strong stimulation of afferent fibers). During my Ph.D thesis we asked whether KARs could also substantially participate to synaptic transmission in more physiological conditions when lower amounts of glutamate are released.
In a first part of this work, we found that indeed KARs can be activated by the quantal release of glutamate as observed during miniature synaptic transmission in CA3 pyramidal cells and CA1 interneurons of the hippocampus. Using pharmacological tools and kinetical characterization we were able to quantify the contribution of KARs to miniature synaptic transmission in these cells and we found that they provide a substantial component of glutamatergic transmission in these conditions. Finally, in CA3 pyramidal cells we found that postsynaptic KARs are selectively co-activated with AMPARs at mossy fiber synapses.
Mossy fibers can sprout in both human patient and animal models of temporal lobe epilepsy (TLE) one of the most common form of epilepsy in humans. This sprouting leads to the formation of an aberrant recurrent excitatory circuit between granule cells (GCs). In a second part of my PhD thesis, we asked whether this sprouting could modify KARs mediated synaptic transmission in granule cells in an animal model of TLE. Our results show that KARs are involved in glutamatergic transmission in granule cells from chronic epileptic rats but not control rats. In these cells, KARs represent half of the glutamatergic excitatory drive and are selectively generated are recurrent mossy fiber synapses. Accordingly, blockade of KARs significantly reduces pathological mossy fiber network-driven activities.
In conclusion, this work shows that KARs as AMPARs can be activated by the quantal release of glutamate. From this starting point, the specific physiological role of KARs in synaptic transmission can be addressed. This work also shows for the first time that aberrant KARs-mediated synapses can be formed under pathological conditions such as TLE. Thus KARs definitely participate to the pathogenesis of temporal lobe epilepsy raising the possibility of designing antiepileptic therapies based on KARs antagonism.
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https://tel.archives-ouvertes.fr/tel-00118689
Contributor : Jérôme Epsztein <>
Submitted on : Wednesday, December 6, 2006 - 10:57:24 AM
Last modification on : Wednesday, July 25, 2018 - 1:23:54 AM
Long-term archiving on: : Tuesday, April 6, 2010 - 8:33:23 PM

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  • HAL Id : tel-00118689, version 1

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Jérôme Epsztein. Rôle des récepteurs kainate dans la transmission synaptique :
une étude dans l'hippocampe de rat contrôle et dans un modèle animal
d'épilepsie du lobe temporal. Neurosciences [q-bio.NC]. Université de Provence - Aix-Marseille I, 2006. Français. ⟨tel-00118689⟩

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