School of Computing, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Yokohama-shi, Kanagawa, 226-8503, Japan.
School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-shi, Tokyo, 192-0392, Japan.
Sci Rep. 2022 Sep 8;12(1):15211. doi: 10.1038/s41598-022-19210-8.
Prepulse inhibition (PPI) is a behavioural phenomenon in which a preceding weaker stimulus suppresses the startle response to a subsequent stimulus. The effect of PPI has been found to be reduced in psychiatric patients and is a promising neurophysiological indicator of psychiatric disorders. Because the neural circuit of the startle response has been identified at the cellular level, investigating the mechanism underlying PPI in Drosophila melanogaster larvae through experiment-based mathematical modelling can provide valuable insights. We recently identified PPI in Drosophila larvae and found that PPI was reduced in larvae mutated with the Centaurin gamma 1A (CenG1A) gene, which may be associated with autism. In this study, we used numerical simulations to investigate the neural mechanisms underlying PPI in Drosophila larvae. We adjusted the parameters of a previously developed Drosophila larvae computational model and demonstrated that the model could reproduce several behaviours, including PPI. An analysis of the temporal changes in neuronal activity when PPI occurs using our neural circuit model suggested that the activity of specific neurons triggered by prepulses has a considerable effect on PPI. Furthermore, we validated our speculations on PPI reduction in CenG1A mutants with simulations.
预备脉冲抑制（PPI）是一种行为现象，其中先前较弱的刺激会抑制后续刺激的惊跳反应。已经发现，精神病患者的 PPI 效应降低，并且是精神障碍的有前途的神经生理学指标。由于惊跳反应的神经回路已经在细胞水平上被确定，因此通过基于实验的数学建模来研究果蝇幼虫中的 PPI 机制可以提供有价值的见解。我们最近在果蝇幼虫中发现了 PPI，并发现 CenG1A 基因突变的幼虫中 PPI 降低，这可能与自闭症有关。在这项研究中，我们使用数值模拟来研究果蝇幼虫中 PPI 的神经机制。我们调整了先前开发的果蝇幼虫计算模型的参数，并证明该模型可以再现几种行为，包括 PPI。使用我们的神经回路模型分析 PPI 发生时神经元活动的时变表明，由预备脉冲触发的特定神经元的活动对 PPI 有很大的影响。此外，我们通过模拟验证了我们对 CenG1A 突变体中 PPI 降低的推测。
