DNA double strand breaks (DSBs) lead to apoptosis or tumorigenesis. The complexity of their repair has led to DSBs being classified as the most harmful type of DNA damage. In a sudden shift, a novel role for DSBs in immediate early gene (IEG) expression, learning, and memory has been suggested. Inducing neuronal activity in vitro and learning events in vivo lead to increases in DSBs and upregulation of IEGs. Additionally, inhibiting DSB repair and increasing DSBs impair long-term memory and alter IEG expression. DNA damage increases and DNA repair decreases with aging; post-mortem tissue from patients diagnosed with mild cognitive impairment or Alzheimer?s disease (AD) in life show increases in DSBs. Altogether, this dissertation adds to the evidence that DSBs have an adaptive function in the brain, and that minor alterations in typical DSB formation and repair can alter IEGs, learning, and memory.