RT Journal Article SR Electronic T1 Endogenous Activation of Kainate Receptors Regulates Glutamate Release and Network Activity in the Developing Hippocampus JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 4473 OP 4484 DO 10.1523/JNEUROSCI.4050-04.2005 VO 25 IS 18 A1 Sari E. Lauri A1 Mikael Segerstråle A1 Aino Vesikansa A1 Francois Maingret A1 Christophe Mulle A1 Graham L. Collingridge A1 John T. R. Isaac A1 Tomi Taira YR 2005 UL http://www.jneurosci.org/content/25/18/4473.abstract AB Kainate receptors (KARs) are highly expressed throughout the neonatal brain, but their function during development is unclear. Here, we show that the maturation of the hippocampus is associated with a switch in the functional role of presynaptic KARs. In a developmental period restricted to the first postnatal week, endogenous l-glutamate tonically activates KARs at CA3 glutamatergic synapses to regulate release in an action potential-independent manner. At synapses onto pyramidal cells, KARs inhibit glutamate release via a G-protein and PKC-dependent mechanism. In contrast, at glutamatergic terminals onto CA3 interneurons, presynaptic KARs can facilitate release in a G-protein-independent mechanism. In both cell types, however, KAR activation strongly upregulates inhibitory transmission. We show that, through the interplay of these novel diverse mechanisms, KARs strongly regulate the characteristic synchronous network activity observed in the neonatal hippocampus. By virtue of this, KARs are likely to play a central role in the development of hippocampal synaptic circuits.