The fast spiking inhibitory interneurons (FSINs) from Dlx5/6+/− animals exhibit abnormal excitability because of a more depolarized spike threshold and broader action potentials. Lu AE98134 (30 μM) increases the excitability of FSINs neurons from normal and Dlx5/6+/− animals by modulating several parameters characteristic for NaV1.1 channels. The selective activation of FSINs by Lu AE98134 restores cognitive flexibility in adult Dlx5/6+/− mice.