Cognitive, Behavioral, and Systems NeuroscienceResearch PaperPositive emotional learning is regulated in the medial prefrontal cortex by GluN2B-containing NMDA receptors

In rats, hedonic ultrasonic vocalizations (USVs) is a validated model of positive affect and is best elicited by rough-and-tumble play. Here we report that modulation of GluN2B-containing NMDA receptors (NMDAR) in the medial prefrontal cortex (MPFC) is involved in positive emotional learning. Rough and tumble play increased both GluN1 and GluN2B NMDAR subunit mRNA and protein levels in the frontal cortex. GLYX-13, a GluN2B-preferring, NMDAR glycine-site partial agonist (1 mg/kg, i.v.) significantly increased positive emotional learning whereas the GluN2B receptor-specific antagonist, ifenprodil (10 mg/kg, i.p.), inhibited positive emotional learning. Animals selectively bred for low rates of hedonic USVs were returned to wild-type levels of positive emotional learning following GLYX-13 treatment. MPFC microinjections of GLYX-13 (0.1-10 μg/side) significantly increased rates of positive emotional learning. Thus GluN2B-containing NMDARs may be involved in positive emotional learning in the MPFC by similar mechanisms as spatial/temporal learning in the hippocampus.

▶Rat hedonic vocalizations were used to examine positive emotional learning (PEL). ▶PEL increased cortical NR1 and NR2B levels. ▶The NR2B partial agonist GLYX-13 increased and an NR2B antagonist decreased PEL. ▶GLYX-13 rescued PEL deficits in rats bred for low rates of hedonic vocalization. ▶Medial prefrontal cortex injections of GLYX-13 increased PEL.