The effect of NMDA receptor antagonism on cortical gamma power and synchronization in vivo

Acute administration of NMDA receptor antagonists such as PCP and ketamine are accepted models of schizophrenia in rats. Oscillatory activity in the gamma range (30-120 Hz) is known to be increased in schizophrenia and by NMDA receptor antagonism. Putative links have been made between abnormal gamma activity and cognitive deficits that are known in schizophrenia. However, the site of action of these antagonists and how they modulate gamma \(in\) \(vivo\) remains unclear. In this study PCP was systemically injected into freely moving rats and ketamine systemically injected into terminally anaesthetised rats, whilst recording intracranial EEG activity in the prefrontal cortex, visual cortex and hippocampus. Ketamine was also administered locally into these same areas in anaesthetised rats and EEG activity recorded. 1 mg/kg PCP significantly decreased performance in an associative learning task, significantly increased gamma power in all recording areas and decreased inter-area gamma synchronisation. 4 mg/kg ketamine also significantly increased gamma power and decreased inter-area synchronisation. Local injection of 5 μg/μl ketamine caused no significant changes to gamma power or inter-area synchronisation. The data presented in this study suggests that local NMDA receptor antagonism may not be the primary cause of changes to gamma activity that occurs following systemic treatments