Subclass imbalance of parvalbumin-expressing GABAergic neurons in the hippocampus of a mouse ketamine model for schizophrenia, with reference to perineuronal nets.

Impairments of parvalbumin-expressing GABAergic neurons (PV neurons) and specialized extracellular structures called perineuronal nets (PNNs) have been found in schizophrenic patients. In this study, we examined potential alterations in four subclasses of PV neurons colocalized with PNNs in the hippocampus of a mouse ketamine model for schizophrenia. Because biosynthesis of human natural killer-1 (HNK-1) is shown to be associated with the risk of schizophrenia, here we used mouse monoclonal Cat-315 antibody, which recognizes HNK-1 glycans on PNNs. Once-daily intraperitoneal injections of ketamine for seven consecutive days induced hyper-locomotor activity in the open field tests. The prepulse inhibition (PPI) test showed that PPI scores declined in ketamine-treated mice compared to vehicle-treated mice. The densities of PV neurons and Cat-315 PNNs declined in the CA1 region of ketamine-treated mice. Interestingly, the density of Cat-315/PV neurons was lower in ketamine-treated mice than in vehicle-treated mice, whereas the density of Cat-315/PV neurons was not affected by ketamine. Among the four subclasses of PV neurons, the densities of Cat-315/PV basket cells and Cat-315/PV axo-axonic cells were lower in ketamine-treated mice than in vehicle-treated mice, while the densities of Cat-315/PV basket cells and Cat-315/PV axo-axonic cells were not affected by ketamine. Taken together, PNNs may not play a simple neuroprotective role against ketamine. Because different subclasses of PV neurons are considered to play distinct roles in the hippocampal neuronal network, the ketamine-induced subclass imbalance of PV neurons may result in abnormal network activity, which underlies the pathophysiology of schizophrenia.