Regulation of the brain’s spatial representation system by DNA-glycosylases removing oxidative DNA lesions

DNA glycosylases play a key role in base excision repair (BER), which is the major pathway for repair the oxidative DNA damage. Recent findings identified that loss of DNA glycosylases responsible for repair of oxidized bases results in impaired brain development, cognition and behavior. Moreover, the transcriptomic analysis in the hippocampus of those DNA glycosylase-deficient transgenic mice showed patterned perturbation of genetic and epigenetic programming. Hippocampal networks encode episodic memories as sequence of events and places according to individual experiences, among which spatial memory is the important one that relates to spatial locations. The identification of place cells in the hippocampus and grid cells in the entorhinal cortex that respond to the animal’s self-localization in any novel environment has been well characterized, which indicates that space information can be encoded and manipulated in the firing pattern of particular neurons. However, the molecular and cellular mechanism underlying how genetic and epigenetic programming affects hippocampal spatial memory remains largely unknown. To bridge the relationship between DNA repair system and hippocampal space memory circuit, we are going to characterize different glycosylase-knockout mice by combining spatial behavior tasks with single-unit extracellular recording of various hippocampal spatial cell types. In this study, we wish to use the following mouse models: Neil1 KO, Neil2 KO, Neil3 KO, Ogg1 KO, Muty KO, OGG/Muty DO KO, Neil1/Neil2 DO KO, and C57/bl6N as a control for all KO model, since our previous work has already implicated that these KO mouse models showed defective learning and memory.