Improvement in Pattern Separation by Regulating Neurogenesis in Hippocampal Culture

Abstract

SUMMARYThe newly generated neurons in adult animals are known to enhance the pattern separation capability. However, it remains unclear how the newborn neurons change the activity patterns in neuronal networks during pattern separation. To verify the change of whole neuronal network activity, the in vitro neurogenesis model is useful because it can be observed and controlled. To develop the in vitro neurogenesis model, we modulated the amount of newly generated neurons in cultures by applying basic fibroblast growth factor (bFGF) or cytarabine (Ara‐C). To investigate the pattern separation capability, the neural cultures were tetanized with two spatial‐pattern stimuli, and then the changes in neural response evoked by different patterns were evaluated using a microelectrode array. We confirmed that the doublecortin expression in cultures with bFGF was more upregulated than the culture with Ara‐C, indicating that bFGF promoted neurogenesis. We found that the enhanced neurogenesis contributed the clusters of neuronal networks to specialize their responses to one of two spatial‐pattern stimuli after tetanization, while the entire response tended to shift toward the immediately preceding pattern without neurogenesis. These results suggest that the property of newly generated neurons that they only respond to the specific pattern unlike mature neurons enhances the pattern separation capability of the entire network.