Schizophrenia in humans typically develops during and after adolescence; however, the biological underpinning for the specificity of this onset time window remains to be determined. In the present study, we investigated this knowledge gap using our own animal model for schizophrenia. Rodents and monkeys challenged with a cytokine, epidermal growth factor (EGF), as neonates are known to exhibit various behavioral and cognitive abnormalities at the post-pubertal stage. We used the EGF-challenged mice as an animal model for schizophrenia to evaluate the electrophysiological impact of this modeling on nigral dopamine neurons before and after puberty. In vivo single unit recording revealed that the burst firing of putative dopamine neurons in substantia nigra pars compacta was significantly higher in the post-pubertal stage of the EGF model than in that of control mice; in contrast, this difference was not observed in the pre-pubertal stage. The increase in burst firing was accompanied by a decline in Ca²⁺-activated K⁺ (I_SK) currents, which influence the firing pattern of dopamine neurons. In vivo local application of the SK channel blocker apamin (80 μM) to the substantia nigra was less effective at increasing burst firing in the EGF model than in control mice, suggesting the pathologic role of the I_SK decrease in this model. Thus, these results suggest that the aberrant post-pubertal hyperactivity of midbrain dopaminergic neurons is associated with the temporal specificity of the behavioral deficit of this model, and support the hypothesis that this dopaminergic aberration could be implicated in the adolescent onset of schizophrenia.

人类的精神分裂症通常在青春期和青春期之后发展。然而，这一发病时间窗特异性的生物学基础仍有待确定。在本研究中，我们使用我们自己的精神分裂症动物模型调查了这一知识差距。啮齿动物和猴子受到细胞因子表皮生长因子 (EGF) 的攻击，因为已知新生儿在青春期后阶段表现出各种行为和认知异常。我们使用受 EGF 攻击的小鼠作为精神分裂症的动物模型，以评估该模型对青春期前后黑质多巴胺神经元的电生理影响。体内单单元记录显示，黑质致密部中假定的多巴胺神经元突然放电在 EGF 模型的青春期后阶段显着高于对照小鼠；相反，在青春期前阶段没有观察到这种差异。爆发性放电的增加伴随着 Ca ²⁺激活的 K ⁺ ( I _SK ) 电流的下降，这会影响多巴胺神经元的放电模式。在EGF 模型中，将 SK 通道阻滞剂 apamin (80 μM) 局部应用于黑质在增加爆发性放电方面的效果不如对照小鼠，这表明I _{SK的病理作用}在这个模型中减少。因此，这些结果表明，中脑多巴胺能神经元的异常青春期后多动症与该模型的行为缺陷的时间特异性有关，并支持这种多巴胺能异常可能与青少年精神分裂症发作有关的假设。