A pharmacological investigation of the role of GLUK5-containing receptors in kainate-driven hippocampal gamma band oscillations

Low concentrations of kainate can induce gamma frequency (25–80 Hz) oscillations in hippocampal slices as well as other brain structures in vitro. Little is known, however, about the kainate receptor (KAR) subtypes that underlie this type of rhythmic neuronal network activity. In this study, the role of GLUK5 subunit-containing KARs in kainate-induced hippocampal gamma frequency oscillations was assessed using GLUK5-selective pharmacological ligands. Activation of GLUK5-containing subunits using the selective agonists (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid (ATPA; 0.1–1 μM) or iodowillardiine (0.1–1 μM) failed to induce gamma frequency oscillations in area CA3 of the rat hippocampal slice. Likewise, preincubation with a selective GLUK5 antagonist, (RS)-3-(2-carboxybenzyl)willardiine (UBP296), did not prevent the appearance of gamma oscillations induced by 150 nM kainate. However, addition of UBP296 (10 μM) to hippocampal slices in which kainate-driven gamma oscillations were pre-established resulted in an approximately 50% reduction in gamma frequency power. These effects occurred in the absence of any effect on AMPA receptor-mediated synaptic transmission. Furthermore, carbachol-induced gamma oscillations were also unaffected by application of UBP296. These results suggest that GLUK5-containing KARs are not alone sufficient to generate gamma frequency oscillations, but are involved in maintaining neuronal network activity induced by the actions of kainate at other KARs such as GLUK6.