GluK1 kainate receptors in parvalbumin interneurons modulate cortico-hippocampal network dynamics during social...

The prefrontal cortex orchestrates complex behaviors by communicating with subcortical structures through synchronized oscillations. Here we show that ablation of GluK1 subunit-containing kainate receptors in parvalbumin interneurons (PV INs) disrupts oscillatory dynamics in the cortico-hippocampal circuits mediating social and cognitive behaviors. In control mice, the hippocampus-medial prefrontal cortex (HC-mPFC) circuit displayed elevated theta and gamma oscillation power as well as enhanced functional coupling during interaction with a familiar mouse. Similar circuit dynamics were not observed during interaction with a novel mouse, consistent with the idea that social recognition involves cortico-hippocampal communication. Mice lacking GluK1 in the PV INs (PV-Grik1^-/-) showed defects in cognitive flexibility and social discrimination as well as impaired neurochemical phenotype of PV INs in the HC and mPFC. Electrophysiological recordings in the PV-Grik1^-/- mice revealed elevated theta and gamma oscillation power in both HC and mPFC along with enhanced functional coupling between these brain regions at rest. In contrast to the controls, no changes in the theta and gamma oscillation powers in the HC or mPFC or in the HC-mPFC coupling were detected in the PV-Grik1^-/- mice during social interaction. Our data suggest that impaired functional dynamics in cortico-hippocampal circuits in the PV-Grik1^-/- mice compromise social discrimination and shed light on the neurobiological mechanisms by which GluK1 dysfunction may contribute to neuropsychiatric disorders.