Glia-Dependent Switch of Kainate Receptor Presynaptic Action
Journal of Neuroscience. 2010-01-20; 30(3): 985-995
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1. J Neurosci. 2010 Jan 20;30(3):985-95. doi: 10.1523/JNEUROSCI.3389-09.2010.
Glia-dependent switch of kainate receptor presynaptic action.
Bonfardin VD(1), Fossat P, Theodosis DT, Oliet SH.
(1)Inserm U 862, Neurocentre Magendie, 33077 Bordeaux France.
Presynaptic kainate receptors (KARs) exert a modulatory action on transmitter
release. This effect can be switched from facilitation to inhibition by an
increased concentration of KAR agonists. We here report that activation of
presynaptic GluK1-containing KARs facilitates GABA release on oxytocin and
vasopressin neurons in the supraoptic nucleus of the hypothalamus. Increase in
ambient levels of glutamate associated with the physiological reduction of
astrocytic coverage of oxytocin neurons in lactating rats switches this
KAR-mediated facilitation to inhibition of GABAergic transmission. This effect
was reproduced in both oxytocin and vasopressin neurons of virgin rats when
glutamate transporters were blocked pharmacologically, thereby establishing that
enhanced levels of extracellular glutamate induce the switch in KAR-mediated
action. The facilitation of GABA release was inhibited with philanthotoxin, a
Ca(2+)-permeable KAR antagonist, suggesting that this effect was associated with
an ionotropic mode of action. Conversely, KAR-mediated inhibition was compromised
in the presence of U73122, a phospholipase C inhibitor, in agreement with the
involvement of a metabotropic pathway. We thus reveal that physiological
astrocytic plasticity modifies the mode of action of presynaptic KARs, thereby
inversing their coupling with GABA release.
PMID: 20089907 [Indexed for MEDLINE]