The medial prefrontal cortex (mPFC} and hippocampus (HPC} are central to executive control, spatial learning and working memory. In order to enable behavioral control, the function of the mPFC and HPC is tuned by complex interplay between excitatory (glutamatergic) and inhibitory (GABAergic) neurotransmitter systems. This thesis has employed lesions, pharmacological and optogenetic methodologies to investigate how the relationship between excitation and inhibition within the adult mouse mPFC and HPC affects cognition, using a battery of touchscreen-based operant assays: the automated spatial array task (ASAT), Spatial Reversal (SR) and Visual Discrimination (VD). Behavioral testing following excitotoxic lesions showed that the HPC was strongly implicated in the performance of both spatial tests (ASAT and SR), while removal of the mPFC had only marginal effects on learning with several trends that did not reach significance. Additionally, in VD, effects were only present as trends towards an involvement of the mPFC in formations of new stimulus-reward relationships. Interdependent processing spanning the mPFC and HPC while not directly assessed can be considered likely to explain complex changes in task performance. Using the described assays helped validate their application to test mPFC and HPC function in mice.