Differential expression of immediate early genes Zif268 and c-Fos in the hippocampus and prefrontal cortex following spatial learning and glutamate receptor antagonism

•NMDAR blockade alters basal levels of c-Fos expression in a region specific manner.•Inhibition of NMDARs, but not AMPARs, disrupts spatial memory encoding.•Inhibition of NMDARs attenuates expression of Zif268 but not c-Fos in area CA1.•AMPAR blockade has no effect on spatial memory acquisition or IEG expression.•Zif268 and c-Fos expression are not coordinated during spatial memory formation.

The objective of this study was to examine the effects of NMDAR and AMPAR antagonism on the expression of Zif268 and c-Fos in the hippocampus and medial prefrontal cortex during spatial memory encoding in rats trained in the Morris water maze. NMDAR inhibition impaired navigation and significantly attenuated expression of Zif268, but not c-Fos, in area CA1. AMPAR channel blockade had little effect on learning or IEG expression. Overall, Zif268 and c-Fos displayed markedly different patterns of hippocampal and prefrontal expression, with Zif268 being more closely linked to spatial learning.