Inhibition of kainate receptors reduces the frequency of hippocampal theta oscillations

JR Huxter, LE Zynyuk, EvL Roloff, VRJ Clarke, NP Dolman, JC-A More, DE Jane, GL Collingridge, RL Muller

Research output: Contribution to journalArticle (Academic Journal)

23 Citations (Scopus)

Abstract

We investigated the role of kainate receptors in the generation of theta oscillations using (S)-1-(2-amino-2-carboxyethyl)-3-(2-carboxythiophene-3-yl-methyl)pyrimidine-2,4-dione (UBP304), a novel, potent and highly selective antagonist of GLUK5-containing kainate receptors. EEG and single-unit recordings were made from the dorsal hippocampus of awake, freely moving rats trained to forage for food. Bilateral intracerebroventricular injections of UBP304 (2.0 µl, two times; 2.08 mM) caused a clear (~25%) reduction in theta frequency that was dissociable from behavioral effects of the drug. The locations of firing fields of principal cells in the hippocampal formation were generally preserved, but both field firing rates and the precision of field organization decreased. UBP304 lowered the frequency of the theta modulation of hippocampal interneuron discharge, accurately matching the reduced frequency of the theta field oscillation. UBP308 [(R)-1-(2-amino-2-carboxyethyl)-3-(2-carboxythiophene-3-yl-methyl)pyrimidine-2,4-dione], the inactive enantiomer of UBP304, caused none of these effects. Our results suggest that GLUK5 receptors have an important role in modulating theta activity. In addition, the effects on cellular responses provide both insight into the mechanisms of theta pacing, and useful information for models of temporal coding.
Translated title of the contributionInhibition of kainate receptors reduces the frequency of hippocampal theta oscillations
Original languageEnglish
Pages (from-to)2212 - 2223
Number of pages12
JournalJournal of Neuroscience
Volume27 (9)
DOIs
Publication statusPublished - Feb 2007

Bibliographical note

Publisher: Society for Neuroscience

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