Neurogenesis Enhances Response Specificity to Spatial Pattern Stimulation in Hippocampal Cultures

Yukimi Tanaka, Takuya Isomura, Kenta Shimba, Kiyoshi Kotani, Yasuhiko Jimbo

Abstract: Objective: Adult neurogenesis in the hippocampus facilitates cognitive functions such as pattern separation in mammals. However, it remains unclear how newborn neurons mediate changes in neural networks to enhance the pattern separation ability. Here, we developed an in vitro model of adult neurogenesis using rat hippocampal cultures in order to investigate whether newborn neurons can be directly incorporated into neural networks related to pattern separation to produce functional improvements. Method: We optimized at schedule of basic fibroblast growth factor (bFGF) administration to enhance neurogenesis, and then used a microelectrode array system to evaluate the responses of neural cultures to two different spatial pattern stimuli (L and inverted L shapes) before and after training. Results: We found that early synaptic response times to a given pattern were shortened after training, and that this effect was more pronounced in cultures treated with bFGF. Furthermore, bFGF-treated cultures showed improved response specificity after training as indicated by calculated Kullback-Leibler divergence values, suggesting that pattern separation was better achieved in cultures with enhanced neurogenesis. Conclusion: Neural networks containing greater numbers of immature neurons exhibited higher response specificity to spatial pattern stimulation, suggesting the improvement of the pattern separation by neurogenesis enhancement. Significance: These results are the first in vitro demonstration that neurogenesis improves pattern separation. Our novel in vitro system will be a useful tool for investigating the contribution of adult neurogenesis to cognitive functions.