Generation of dentate granule neurons in the hippocampus peaks during the early postnatal period and continues throughout life (Angevine, 1965). DISC1 expression in the dentate gyrus starts from embryonic stages and is maintained in adulthood (Austin et al., 2004). To assess whether DISC1 also regulates early postnatal hippocampal neurogenesis, we stereotaxically injected retroviruses expressing shRNA-D1 or shRNA-C1 into the dentate gyrus at postnatal day 10 (P10; Figure 3A). Consistent with previous results (Zhao et al., 2006), time course analysis showed that shRNA-C1/GFP+ newborn neurons in the early postnatal hippocampus exhibited significantly accelerated dendritic development compared to those in the adult brain (Figure 3B). Notably, shRNA-D1/GFP+ neurons in the early postnatal hippocampus did not exhibit any accelerated dendritic growth when compared to those expressing shRNA-C1 (Figures 3A, 3B and S3A). Furthermore, there was no significant difference in the soma size, primary dendrite number, or neuronal positioning at time points examined (Figures 3C to 3E). Expression of shRNA-C1 or shRNA-D1 also did not affect neuronal subtype differentiation of neural progenitors into Prox1+ dentate granule neurons (Figure S3B). Taken together, these results show that development of the same neuronal subtype exhibits differential DISC1-dependency during early postnatal and adult hippocampal neurogenesis.
