Department of Anatomy & Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Neurotox Res. 2010 Nov;18(3-4):306-12. doi: 10.1007/s12640-010-9157-3. Epub 2010 Feb 12.
Dopamine is a critical modulator of prefrontal cortical function, and it is known to be dysfunctional in schizophrenia. Current hypotheses on schizophrenia highlight developmental aspects and genetic predisposition for the disease; yet, symptom onset typically occurs during adolescence. Several aspects of prefrontal cortical circuits and their modulation by dopamine mature postnatally, as late as during adolescence. Here we review studies assessing the postnatal trajectory of dopamine control of GABA interneurons, a neuronal population that has been long suspected to be critical for schizophrenia pathophysiology. Dopamine modulation of fast-spiking interneurons changes dramatically during adolescence (postnatal day 45-50 in rats) with D2 agonists switching from being mildly inhibitory in prepubertal rats to strongly excitatory in young adult rats. In vivo recordings in adult rats reveal that deep-layer pyramidal neurons respond to endogenous DA release with suppression of firing while interneurons are activated. In adult rats with a neonatal ventral hippocampal lesion (NVHL), an extensively studied developmental model of schizophrenia, the maturation in the D2 modulation of interneuron physiology fails to occur, rendering a disinhibited prefrontal cortex. Abnormal interneuron maturation may therefore impair cognitive function in the adult animal.
多巴胺是前额皮质功能的关键调节因子，已知其在精神分裂症中存在功能障碍。目前关于精神分裂症的假说强调了疾病的发展方面和遗传易感性；然而，症状通常在青春期出现。前额皮质回路及其多巴胺调制的几个方面在出生后发育成熟，直到青春期。在这里，我们回顾了评估多巴胺对 GABA 中间神经元控制的出生后轨迹的研究，GABA 中间神经元一直被怀疑是精神分裂症病理生理学的关键。多巴胺对快速放电中间神经元的调制在青春期（大鼠出生后第 45-50 天）发生剧烈变化，D2 激动剂在青春期前大鼠中表现出轻微抑制作用，而在年轻成年大鼠中表现出强烈兴奋作用。在成年大鼠中进行的体内记录显示，内源性 DA 释放会抑制深层锥体神经元的放电，而中间神经元被激活。在患有新生海马腹侧损伤（NVHL）的成年大鼠中，NVHL 是一种广泛研究的精神分裂症发育模型，中间神经元生理学中 D2 调节的成熟未能发生，导致前额皮质去抑制。因此，中间神经元的异常成熟可能会损害成年动物的认知功能。
