title: Endogenous activation of kainate receptors regulates glutamate release and network activity in the developing hippocampus.
abstract: 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.
authors.affiliation: Neuroscience Center and Department of Biological and Environmental Sciences, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Sari E
authors.initials: SE
authors.lastname: Lauri
authors.forename: Mikael
authors.initials: M
authors.lastname: Segerstråle
authors.forename: Aino
authors.initials: A
authors.lastname: Vesikansa
authors.forename: Francois
authors.initials: F
authors.lastname: Maingret
authors.forename: Christophe
authors.initials: C
authors.lastname: Mulle
authors.forename: Graham L
authors.initials: GL
authors.lastname: Collingridge
authors.forename: John T R
authors.initials: JT
authors.lastname: Isaac
authors.forename: Tomi
authors.initials: T
authors.lastname: Taira
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000494:pharmacology; D001418:Baclofen / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000528:radiation effects; D005663:Furans / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D007546:Isoquinolines / Q000494:pharmacology; D007555:Isoxazoles / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D018345:Mice, Knockout; D009415:Nerve Net / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D010852:Picrotoxin / Q000494:pharmacology; D011336:Probability; D018092:Kainic Acid Receptors / Q000172:deficiency / Q000502:physiology*
chemical_list: D001224:Aspartic Acid; D001418:Baclofen; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D005663:Furans; D018755:GABA Agonists; D018756:GABA Antagonists; D018698:Glutamic Acid; D006160:Guanosine Triphosphate; D007546:Isoquinolines; D007555:Isoxazoles; D010852:Picrotoxin; D018092:Kainic Acid Receptors; C113170:2-Fu-AMPA; C400802:LY382884; C120673:benzyloxyaspartate