Neuronal activity and the concomitant production of metabolic acids can vary enormously. Mechanisms for acid extrusion are therefore critical for neuronal homeostasis. Different members of the Slc4a family of bicarbonate transporters are expressed in neurons. To study their role for neuronal acitivity in more detail, we generated mouse models with a targeted disruption of the Na+ independent anion-exchanger Ae3 and the Na+ dependent anion-exchangers NCBE and NDCBE. The analysis of these mouse models unraveled important functions of these transporters both at the level of the neuronal network and synaptic transmission.