Laboratory of Neurochemistry and Behavior, Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri" Milano, Italy.
Front Neural Circuits. 2014 Jun 11;8:58. doi: 10.3389/fncir.2014.00058. eCollection 2014.
Executive functions are an emerging propriety of neuronal processing in circuits encompassing frontal cortex and other cortical and subcortical brain regions such as basal ganglia and thalamus. Glutamate serves as the major neurotrasmitter in these circuits where glutamate receptors of NMDA type play key role. Serotonin and dopamine afferents are in position to modulate intrinsic glutamate neurotransmission along these circuits and in turn to optimize circuit performance for specific aspects of executive control over behavior. In this review, we focus on the 5-choice serial reaction time task which is able to provide various measures of attention and executive control over performance in rodents and the ability of prefrontocortical and striatal serotonin 5-HT1A, 5-HT2A, and 5-HT2C as well as dopamine D1- and D2-like receptors to modulate different aspects of executive and attention disturbances induced by NMDA receptor hypofunction in the prefrontal cortex. These behavioral studies are integrated with findings from microdialysis studies. These studies illustrate the control of attention selectivity by serotonin 5-HT1A, 5-HT2A, 5-HT2C, and dopamine D1- but not D2-like receptors and a distinct contribution of these cortical and striatal serotonin and dopamine receptors to the control of different aspects of executive control over performance such as impulsivity and compulsivity. An association between NMDA antagonist-induced increase in glutamate release in the prefrontal cortex and attention is suggested. Collectively, this review highlights the functional interaction of serotonin and dopamine with NMDA dependent glutamate neurotransmission in the cortico-striatal circuitry for specific cognitive demands and may shed some light on how dysregulation of neuronal processing in these circuits may be implicated in specific neuropsychiatric disorders.
执行功能是前额皮质和基底神经节、丘脑等皮质和皮质下脑区等回路中神经元处理的新兴特性。谷氨酸是这些回路中的主要神经递质，其中 NMDA 型谷氨酸受体发挥关键作用。血清素和多巴胺传入神经能够调节这些回路中的内在谷氨酸神经传递，从而优化回路性能，以实现行为的特定方面的执行控制。在这篇综述中，我们重点介绍了 5 选择序列反应时间任务，该任务能够在啮齿动物中提供注意力和执行控制性能的各种测量，并能够调节前额皮质和纹状体中的血清素 5-HT1A、5-HT2A 和 5-HT2C 以及多巴胺 D1-和 D2-样受体，以调节 NMDA 受体功能低下引起的前额叶皮层执行和注意力障碍的不同方面。这些行为研究与微透析研究的结果相结合。这些研究说明了血清素 5-HT1A、5-HT2A、5-HT2C 和多巴胺 D1-但不是 D2-样受体对注意力选择性的控制，以及这些皮质和纹状体中的血清素和多巴胺受体对不同方面的执行控制的独特贡献，例如冲动性和强迫性。提示 NMDA 拮抗剂诱导的前额叶皮层谷氨酸释放增加与注意力有关。总的来说，这篇综述强调了血清素和多巴胺与 NMDA 依赖性谷氨酸能神经传递在皮质-纹状体回路中的功能相互作用，以满足特定的认知需求，并可能为这些回路中神经元处理的失调如何与特定的神经精神障碍有关提供一些线索。
