Distinct roles for the kainate receptor subunits GluR5 and GluR6 in kainate-induced hippocampal gamma oscillations.
Kainate receptors (KARs) play an important role in synaptic physiology, plasticity, and pathological phenomena such as epilepsy. However, the physiological implications for neuronal networks of the distinct expression patterns of KAR subunits are unknown. Using KAR knock-out mice, we show that subunits glutamate receptor (GluR) 5 and GluR6 play distinct roles in kainate-induced gamma oscillations and epileptiform burst activity. Ablation of GluR5 leads to a higher susceptibility of the network to the oscillogenic and epileptogenic effects of kainate, whereas lack of GluR6 prevents kainate-induced gamma oscillations or epileptiform bursts. Based on experimental and simulated neuronal network data as well as the consequences of GluR5 and GluR6 expression for cellular and synaptic physiology, we propose that the functional interplay of GluR5-containing KARs on axons of interneurons and GluR6-containing KARs in the somatodendritic region of both interneurons and pyramidal cells underlie the oscillogenic and epileptogenic effects of kainate.
Fisahn
André
A
Laboratory of Cellular and Synaptic Neurophysiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Andre.Fisahn@neuro.ki.se
Contractor
Anis
A
Traub
Roger D
RD
Buhl
Eberhard H
EH
Heinemann
Stephen F
SF
McBain
Chris J
CJ
D000818:Animals; D001369:Axons / Q000502:physiology; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D007395:Interneurons / Q000502:physiology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000502:physiology; D009991:Oscillometry; D011493:Protein Kinase C / Q000502:physiology; D017966:Pyramidal Cells / Q000502:physiology; D018092:Kainic Acid Receptors / Q000819:agonists / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D000097806:GluK2 Kainate Receptor
D018691:Excitatory Amino Acid Antagonists; D007608:Kainic Acid; D011493:Protein Kinase C; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor