Regulation and dysregulation of neuronal circuits by KARs.
Neuropharmacology. 2021-10-01; 197: 108699
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(1)Univ. Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, IINS, UMR
5297, F-33000, Bordeaux, France. Electronic address:
(2)INMED, INSERM UMR1249, Aix-Marseille Université, Marseille, France.
Kainate receptors (KARs) constitute a family of ionotropic glutamate receptors
(iGluRs) with distinct physiological roles in synapses and neuronal circuits.
Despite structural and biophysical commonalities with the other iGluRs, AMPA
receptors and NMDA receptors, their role as post-synaptic receptors involved in
shaping EPSCs to transmit signals across synapses is limited to a small number
of synapses. On the other hand KARs regulate presynaptic release mechanisms and
control ion channels and signaling pathways through non-canonical metabotropic
actions. We review how these different KAR-dependent mechanisms concur to
regulate the activity and plasticity of neuronal circuits in physiological
conditions of activation of KARs by endogenous glutamate (as opposed to
pharmacological activation by exogenous agonists). KARs have been implicated in
neurological disorders, based on genetic association and on physiopathological
studies. A well described example relates to temporal lobe epilepsy for which
the aberrant recruitment of KARs at recurrent mossy fiber synapses takes part in
epileptogenic neuronal activity. In conclusion, KARs certainly represent an
underestimated actor in the regulation of neuronal circuits, and a potential
therapeutic target awaiting more selective and efficient genetic tools and/or
ligands. This article is part of the special Issue on ‘Glutamate Receptors –
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