Mutations of one or more of the mitochondrial respiratory chain enzymes might cause mitochondrial dysfunction and increased generation of reactive oxygen species (ROS), which are assumed to be key players in neurodegeneration. However, the causal relationship between mitochondrial dysfunction, oxidative stress and synaptic dysfunction is not clearly understood. While ROS contributes to age-related impairment in learning and memory, it has also been demonstrated that ROS are physiological components of signal transduction. To investigate the role of ROS production as a function of respiratory chain proteins, we used conplastic mouse strains with stable mutations of mitochondrial genes associated with respiration. In these strains, we measured ROS levels in different age groups using MitoSox Red, an indicator for superoxide. We found that production of superoxide saturated at the age of 6 months. In parallel with ROS measurements, we also studied cognitive function by testing spatial learning ability in Morris-water-maze performance in vivo, and by measurements of synaptic plasticity via long-term potentiation in vitro. Indeed, we found that 3-month-old mice harboring a mutation in complex I, III or IV seemed to have reduced synaptic plasticity in CA1 and neocortex. In contrast, mice with mutations in complex V, which was not assumed to lead to enhanced ROS production, showed intact synaptic plasticity. However, impairment of LTP induction and altered ROS production were not associated with behavioral changes in these mice. In conclusion, our data strongly suggest that ROS production influences synaptic plasticity.