Sex dimorphic role of NMDA receptors in hippocampal-dependent spatial memory and plasticity during juvenility

Juvenility (early life) is the crucial stage of neurodevelopment, as the alterations made during this time have been linked to long-term effects on cognition. The brain undergoes significant remodelling involving dendritic arborization, synaptogenesis and neuron proliferation within and between areas, particularly in the hippocampus, which plays a vital role in spatial memory processing. Spatial memory processing ability continues to develop alongside hippocampal maturation particularly before puberty. The N-methyl-d-aspartate (NMDA) type of glutamate receptor channel is essential for activity-dependent synaptic plasticity and spatial memory formation in both rodents and humans. However, limited studies have addressed the role of NMDA receptors (NMDAr) in spatial memory of juveniles. In this study, we aimed to investigate the role the NMDAr in juvenile rats of both male and female in spatial memory and plasticity using behavioral, pharmacological, and electrophysiological approaches. Our results demonstrate that systemic administration of NMDAr antagonist, MK801, significantly impairs long-term spatial memory and long-term potentiation (LTP) in the hippocampal CA1 in juvenile males without an effect on juvenile females. Taken together our results revealed a sex dimorphic role of NMDAr in the spatial memory and plasticity during juvenility. These sex-specific differences in the mechanisms of spatial memory and plasticity may call for gender-specific attention in spatial cognitive related disorders in children.