The role of desmoplakin for neuronal function in the dentate gyrus and anxiety-related behavior

Desmoplakin (Dsp) is a component of desmosomal cell-cell junctions. In the central nervous system, Dsp is specifically expressed in the hippocampal dentate gyrus (DG). However, it is unclear how Dsp impacts hippocampal function and its related behaviors. In this study, we provide evidence that Dsp in the DG maintains hippocampal functions, including neuronal activity and adult neurogenesis, and contributes to anxiolytic-like effects using an adeno-associated virus knockdown system in male mice. Dsp knockdown in the DG resulted in a lowered expression of an activity-dependent transcription factor FosB and reduction of serotonin responsiveness at the DG mossy fiber synapses. In addition, the suppression of Dsp impairs adult neurogenic processes in the DG. Moreover, DG-specific Dsp knockdown mice showed an increase in anxiety-like behaviors. Taken together, this research suggests that Dsp in the DG may function as a regulator to maintain proper neuronal activation and contribute to the adaptation of emotion-related behavior. ### Competing Interest Statement The authors have declared no competing interest.