High levels of oxidative stress are a common aspect of most neurodegenerative disorders. Oxidative stress in the brain causes DNA lesions that are mainly repaired by the base excision repair (BER) pathway. The BER pathway is initiated by specialized DNA glycosylases, such as the Neil gene family of endonuclease VIII-like glycosylases. The Neil3 glycosylase has not been well characterized and very little is known about its function. Previous works indicate that the Neil3 gene product may work as a DNA glycosylase due to its sequence homology and structural similarity to the other Neil genes, while others indicate that it may be in involved in progenitor cell differentiation and neuronal development. Neurodegenerative disorders are known to affect the hippocampal formation leading to impairment in learning and memory. Signal transmission within the hippocampal formation is relayed through excitatory and inhibitory synapses. Glutamate is the main excitatory neurotransmitter in the central nervous system (CNS), and activates the N-methyl-D-aspartate (NMDA) receptor within the excitatory synapses. The NMDA receptor is influential in the regulation of neurogenesis, as well as the induction of long-term potentiation (LTP) and long-term depression (LTD) within the hippocampus. Immunohistochemical techniques were used in order to determine if the absence of the Neil3 gene would affect the development of the excitatory synapses within the hippocampal formation as mice age. Specifically, alterations to the synaptic morphology and receptor expression within the excitatory synapses were examined in wild type (WT) mice and Neil3 knock-out (KO) mice as they went from mature to aged. Through the use of confocal immunofluorescence microscopy it was shown that the NMDA receptor expression is upregulated in various regions of the hippocampal formation in mice lacking the Neil3 gene. The quantitative electron microscopy showed no differences between mature WT mice and Neil3 KO mice, but as the mice aged alterations in the synapse morphology and receptor expression became evident. Comapred to the aged WT mice, the aged Neil3 KO mice showed a decrease in the length of their post synaptic densities (PSD), i.e. in the size of the post synaptic membrane overlaying the PSD, as well as an increase in the density of NMDA receptor subunits NR1 and NR2A/B within the PSD of the excitatory synapses. The results show that as Neil3 KO mice become aged, they develop alterations to the synaptic morphology and the NMDA receptor expression in the excitatory synapses within the hippocampal formation. The alterations may indicate a compensatory effect taking place within the excitatory synapses in order to maintain normal and optimal synaptic function within the hippocampal formation of aged mice lacking the Neil3 gene.