Functional GluR6 kainate receptors in the striatum: indirect downregulation of synaptic transmission.
Kainate receptors (KARs) are abundantly expressed in the basal ganglia, but their function in synaptic transmission has not been established. In the present study, we show that the GluR6 subunit of KARs is expressed in both substance P- and enkephalin-containing GABAergic projection neurons of the mouse striatum. Using whole-cell voltage-clamp recordings in brain slices, we demonstrate the presence of functional KARs in the dorsal striatum activated by low concentrations of the AMPA/KAR agonist domoate in wild-type but not GluR6-deficient mice. Despite the abundance of KARs, we found no evidence for synaptic activation of these receptors after single or repetitive stimulation of glutamatergic afferents. Domoate induces a transient increase in the frequency of spontaneous IPSCs of small amplitude and a sustained depression of large IPSCs evoked by minimal electrical stimulation within the striatum in wild-type mice but not in GluR6-deficient mice. This depressant effect is inhibited in presence of adenosine A(2A) receptor antagonists, ZM-241385 and SCH-58261. These data strongly suggest that, in striatal neurons, KARs depress GABAergic synaptic transmission indirectly via release of adenosine acting on A(2A) receptors.
Chergui
K
K
Centre National de la Recherche Scientifique, Unite Mixte Recherche 5091, Université Victor Segalen-Bordeaux II, 33076 Bordeaux Cedex, France.
Bouron
A
A
Normand
E
E
Mulle
C
C
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000737:chemistry* / Q000166:cytology / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D009474:Neurons / Q000737:chemistry / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D018092:Kainic Acid Receptors / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology; D000097806:GluK2 Kainate Receptor
D001569:Benzodiazepines; D018691:Excitatory Amino Acid Antagonists; D007608:Kainic Acid; D009467:Neuromuscular Depolarizing Agents; D011810:Quinoxalines; D012333:RNA, Messenger; D018341:Receptors, Adrenergic, alpha-2; D018092:Kainic Acid Receptors; D005680:gamma-Aminobutyric Acid; D000097806:GluK2 Kainate Receptor; C547769:Adra2a protein, mouse; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C079692:GYKI 53655; C012301:domoic acid