In the developing rat hippocampus, endogenous activation of presynaptic kainate receptors reduces GABA release from mossy fiber terminals.
Presynaptic kainate receptors regulate synaptic transmission in several brain areas but are not known to have this action at immature mossy fiber (MF) terminals, which during the first week of postnatal life release GABA, which exerts into targeted cells a depolarizing and excitatory action. Here, we report that, during the first week of postnatal life, endogenous activation of GluK1 receptors by glutamate present in the extracellular space severely depresses MF-mediated GABAergic currents [GABA(A)-mediated postsynaptic currents (GPSCs)]. Activation of GluK1 receptors was prevented by treating the slices with enzymatic glutamate scavengers that enhanced the clearance of glutamate from the extracellular space. The depressant effect of GluK1 on MF-GPSCs was mediated by a metabotropic process sensitive to pertussis toxin. In the presence of U73122 (1-[6-[[(17b)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione), a selective inhibitor of phospholipase C, along the transduction pathway downstream to G-protein, GluK1 activation increased the probability of GABA release, thus unveiling the ionotropic action of this receptor. In line with this type of action, we found that GluK1 enhanced MF excitability by directly depolarizing MF terminals via calcium-permeable cation channels. Furthermore, GluK1 dynamically regulated the direction of spike time-dependent plasticity occurring by pairing MF stimulation with postsynaptic spiking and switched spike time-dependent potentiation into depression. The GluK1-induced depression of MF-GPSCs would prevent excessive activation of the CA3 associative network by the excitatory action of GABA and the emergence of seizures in the immature brain.
Neuroscience Programme, International School for Advanced Studies, 34014 Trieste, Italy.
Maddalena D
MD
Caiati
Sudhir
S
Sivakumaran
Enrico
E
Cherubini
D000200:Action Potentials; D000818:Animals; D015536:Down-Regulation; D004789:Enzyme Activation; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000254:growth & development*; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018092:Kainic Acid Receptors / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018698:Glutamic Acid; D018092:Kainic Acid Receptors; D005680:gamma-Aminobutyric Acid