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Chunk #18 — RESULTS — Early Postnatal and Adult Hippocampal Neurogenesis Exhibit Differential Tempo in Shifting the Polarity of GABA Responses

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Interplay between DISC1 and GABA signaling regulates neurogenesis in mice and risk for schizophrenia.
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We then performed Ca2+ imaging analysis of new neurons during early postnatal neurogenesis after retroviral labeling at P10 (Figure 4C). While muscimol induced a large Ca2+ rise in new neurons at 3 dpi, the peak Ca2+ responses were significantly decreased by 7 dpi and largely diminished by 11 dpi (Figure 4D). Thus, there is an accelerated tempo in the polarity shift of GABAergic responses by new neurons during early postnatal neurogenesis when compared to adult neurogenesis. Consistent with our model that DISC1 functions downstream of Ca2+ signaling (Figure 2L), DISC1 KD did not significantly affect muscimol-induced Ca2+ responses in new neurons during early postnatal or adult neurogenesis (Figures 4B and 4D). These results raise the possibility that newborn neurons during early postnatal neurogenesis escape the DISC1 control of GABAergic responses due to a reduced time-window of depolarizing GABA action.