GluK1 kainate receptors are necessary for functional maturation of parvalbumin interneurons regulating amygdala circuit function.

ABSTRACT

Parvalbumin expressing interneurons (PV INs) are key players in the local inhibitory circuits and their developmental maturation coincides with the onset of adult-type network dynamics in the brain. Glutamatergic signaling regulates emergence of the unique PV IN phenotype, yet the receptor mechanisms involved are not fully understood. Here we show that GluK1 subunit containing kainate receptors (KARs) are necessary for development and maintenance of the neurochemical and functional properties of PV INs in the lateral and basal amygdala (BLA). Ablation of GluK1 expression specifically from PV INs resulted in low parvalbumin expression and loss of characteristic high firing rate throughout development. In addition, we observed reduced spontaneous excitatory synaptic activity at adult GluK1 lacking PV INs. Intriguingly, inactivation of GluK1 expression in adult PV INs was sufficient to abolish their high firing rate and to reduce PV expression levels, suggesting a role for GluK1 in dynamic regulation of PV IN maturation state. The PV IN dysfunction in the absence of GluK1 perturbed the balance between evoked excitatory vs. inhibitory synaptic inputs and long-term potentiation (LTP) in LA principal neurons, and resulted in aberrant development of the resting-state functional connectivity between mPFC and BLA. Behaviorally, the absence of GluK1 from PV INs associated with hyperactivity and increased fear of novelty. These results indicate a critical role for GluK1 KARs in regulation of PV IN function across development and suggest GluK1 as a potential therapeutic target for pathologies involving PV IN malfunction.