Treadmill running regulates adult neurogenesis, spatial and non-spatial learning, parvalbumin neuron activity by ErbB4 signaling

In our previous study, we found parvalbumin (PV) positive GABAergic interneurons in DG were critical for exercise to increase adult neurogenesis and to improve schizophrenia related phenotypes in mouse model. How exercise affects PV interneuron function needs to be further investigated. In this study, AG1478, an ErbB4 inhibitor, was used to explore its molecular mechanisms as a pharmacological means. Four weeks post-running with AG1478, we found: (1). AG1478 significantly impaired the performances in T-maze, Morris water maze (MWM, spatial learning and memory), contextual fear conditioning and discrimination learning paradigm (non-spatial working and reference memory). (2).AG1478 enhanced neurogenesis loss, downregulated the expression of p-ErbB4 and total ErbB4 protein, (3) AG1478 decreased the intracellular Ca 2+ levels in PV neurons which could be reversed by running. Taken together, our study suggested that Treadmill running regulates adult neurogenesis, spatial and non-spatial learning, PV neuron activity by ErbB4 signaling.