A Specific Role of Hippocampal NMDA Receptors and Arc Protein in Rapid Encoding of Novel Environmental Representations and a More General Long-Term Consolidation Function

Activation of the NMDA receptor (NMDAR) has been proposed to be a key event responsible for the structural changes that occur in neurons during learning and memory formation. It has been extensively studied yet no consensus has been reached on its mnemonic role as both NMDAR dependent and independent forms of learning have been observed. We investigated the role that hippocampal NMDAR have in rapid spatial learning and memory across training environments. Hippocampal NMDAR was blocked via intra-hippocampal injection of the competitive antagonist CPP. Groups of rats were pre-trained on a spatial version of the Morris water task, and then mass reversal training under NMDAR blockade occurred in the same or different training environments as pre-training. We measured expression of Arc protein throughout the main hippocampal subfields, CA1, CA3, and dentate gyrus, after mass-training. We observed that NMDAR blockade allowed for rapid spatial learning, but not consolidation, when the SUBJECTS used previously acquired environmental information. Interestingly, NMDAR blockade impaired rapid spatial learning when rats were mass-trained in a novel context. Arc protein expression in the dentate gyrus followed this pattern of NMDAR dependent spatial behavior, with high levels of expression observed after being trained in the new environment, and low levels when trained in the same environment. CPP significantly reduced Arc expression in the dentate gyrus. These results implicate dentate NMDAR in the acquisition of novel environmental information.