title: Mechanisms underlying developmental speeding in AMPA-EPSC decay time at the calyx of Held.
abstract: The time course of synaptic conductance is important in temporal precision of information processing in the neuronal network. The AMPA receptor (AMPAR)-mediated EPSCs at the calyx of Held become faster in decay time as animals mature. To clarify how desensitization and deactivation of AMPARs contribute to developmental speeding of EPSCs, we compared the decay time of quantal EPSCs (qEPSCs) with the deactivation and desensitization times of AMPAR currents induced in excised patches by fast glutamate application (AMPA patch currents). Both the deactivation and desensitization times of AMPA patch currents became markedly faster from postnatal day 7 (P7) to P14 and changed little thereafter. In individual neurons, throughout development (P7-P21), the time constants of deactivation and fast desensitization in AMPA patch currents were similar to each other and close to the qEPSC decay time constant. Cyclothiazide (CTZ) abolished the fast desensitization, prolonged deactivation of AMPA patch currents, and slowed the decay time of EPSCs. The effects of CTZ on AMPA patch currents were unchanged throughout development, whereas its effect on EPSCs became weaker as animals matured. In single-cell reverse transcription-PCR analysis, glutamate receptor subunit 4 (GluR4) flop increased from P7 to P14 and changed little thereafter. At P7, the GluR4 flop abundance had an inverse correlation with the qEPSC decay time. These results together suggest that both desensitization and deactivation of AMPARs are involved in the EPSC decay time, but the contribution of desensitization decreases during postnatal development at the calyx of Held.
authors.affiliation: Department of Neurophysiology, University of Tokyo Graduate School of Medicine, Tokyo 113-0033, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Koike-Tani
authors.forename: Naoto
authors.initials: N
authors.lastname: Saitoh
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D001581:Benzothiadiazines / Q000494:pharmacology; D001933:Brain Stem / Q000254:growth & development* / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D017729:Presynaptic Terminals / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013997:Time Factors
chemical_list: D001581:Benzothiadiazines; D012333:RNA, Messenger; D018091:Receptors, AMPA; D018698:Glutamic Acid; C004639:cyclothiazide