Neurodevelopmental psychiatric disorders including schizophrenia (Sz) and attention deficit hyperactivity disorder (ADHD) are chronic mental illnesses, which place costly and painful burdens on patients, their families and society. In recent years, the epidermal growth factor (EGF) family member Neuregulin 1 (NRG1) and one of its receptors, ErbB4, have received considerable attention due to their regulation of inhibitory local neural circuit mechanisms important for information processing, attention, and cognitive flexibility. Here we examine an emerging body of work indicating that either decreasing NRG1–ErbB4 signaling in fast-spiking parvalbumin positive (PV+) interneurons or increasing it in vasoactive intestinal peptide positive (VIP+) interneurons could reactivate cortical plasticity, potentially making it a future target for gene therapy in adults with neurodevelopmental disorders. We propose preclinical studies to explore this model in prefrontal cortex (PFC), but also review the many challenges in pursuing cell type and brain-region-specific therapeutic approaches for the NRG1 system.

包括精神分裂症 (Sz) 和注意力缺陷多动障碍 (ADHD) 在内的神经发育性精神疾病是一种慢性精神疾病，给患者、他们的家庭和社会带来了代价高昂和痛苦的负担。近年来，表皮生长因子 (EGF) 家族成员 Neuregulin 1 (NRG1) 及其受体之一 ErbB4 因其对信息处理、注意力和认知灵活性重要的抑制性局部神经回路机制的调节而受到广泛关注. 在这里，我们研究了一项新兴的工作，表明在快速尖峰小白蛋白阳性 (PV+) 中间神经元中减少 NRG1-ErbB4 信号传导或在血管活性肠肽阳性 (VIP+) 中间神经元中增加它可以重新激活皮质可塑性，可能使其成为神经发育障碍成人基因治疗的未来目标。我们建议进行临床前研究以探索前额叶皮层 (PFC) 中的这种模型，但也回顾了为 NRG1 系统寻求细胞类型和大脑区域特异性治疗方法的许多挑战。