PT  - JOURNAL ARTICLE
AU  - John R. Huxter
AU  - Larissa E. Zinyuk
AU  - Eva v. L. Roloff
AU  - Vernon R. J. Clarke
AU  - Nigel P. Dolman
AU  - Julia C. A. More
AU  - David E. Jane
AU  - Graham L. Collingridge
AU  - Robert U. Muller
TI  - Inhibition of Kainate Receptors Reduces the Frequency of Hippocampal Theta Oscillations
AID  - 10.1523/JNEUROSCI.3954-06.2007
DP  - 2007 Feb 28
TA  - The Journal of Neuroscience
PG  - 2212--2223
VI  - 27
IP  - 9
4099  - http://www.jneurosci.org/content/27/9/2212.short
4100  - http://www.jneurosci.org/content/27/9/2212.full
SO  - J. Neurosci.2007 Feb 28; 27
AB  - 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.