Distinct patterns of DNA methylation (mC) and hydroxymethylation (hmC) are identified in the neuronal epigenome, and the dynamic regulation of mC/hmC is associated with various hippocampus-dependent memory processes. hmC, an oxidized form of mC, acts as an essential intermediate in the active DNA demethylation pathway. The further oxidized hmC derivatives are eventually removed by the thymine DNA glycosylase (TDG) initiated base excision repair (BER). Constitutive knockout or catalytic inactivation of TDG leads to embryonic lethality in mice, demonstrating an essential role of TDG in the epigenetic regulation of early development. However, we do not know whether TDG impacts the epigenetic plasticity and functional identity of terminally differentiated cells such as neurons. It remains elusive whether TDG-dependent removal of mC derivatives is required for the encoding, association, consolidation, and retrieval of distinct memories. In this study, we generated a neuron-specific Tdg knockout mouse model (CamK2a-Tdg-ko) with a pronounced loss of TDG in the hippocampal CA1 neurons. We established different behavioral tasks (e.g., Novel object location task, Reward memory task, Radial Arm Maze, and Fear Trace Conditioning test) to assess hippocampal memories after TDG depletion. We will investigate the functional properties of TDG-deficient CA1 neurons by extracellular neuronal recording experiments. Further, we will isolate TDG-depleted hippocampal neurons for transcriptomic and epigenomic analysis to uncover TDG-dependent epigenetic mechanisms underlying hippocampal function in memory.