Marinelli M, Rudick C N, Hu X-T, White F J
Department of Cellular & Molecular Pharmacology, Rosalind Franklin University of Medicine and Science/The Chicago Medical School, North Chicago, IL 60064, USA.
CNS Neurol Disord Drug Targets. 2006 Feb;5(1):79-97. doi: 10.2174/187152706784111542.
This aim of this chapter is to review literature on the excitability and function of dopamine neurons that originate in the midbrain and project to cortico-limbic and motor structures (A9 and A10 dopamine pathways). Electrophysiological studies on rodent or non-human primates have shown that these dopamine neurons are silent or spontaneously active. The spontaneously active neurons show slow regular firing, slow irregular firing or fast bursting activity. In the first section, we will review how neuronal firing is modulated by intrinsic factors, such as impulse-regulating somatodendritic dopamine autoreceptors, a balance between inward voltage-gated sodium and calcium currents and outward potassium currents. We will then review the major excitatory and inhibitory pathways that play important roles in modulating dopamine cell excitability. In the second section, we will discuss how, in addition to being modulated by intrinsic and synaptic factors, excitability of dopamine neurons can also be modulated by life experiences. Dopamine neurons change their firing rate throughout the developmental period, their activity can be modified by stressful life events, and the firing mode can change as a consequence of acute or repeated exposure to psychoactive drugs. Finally, these cells change their firing pattern in response to behaviorally relevant stimuli and learning experiences. We will conclude by discussing how changes in the physiology of the dopamine neurons could participate in the development or exacerbation of psychiatric conditions such as drug addiction.
本章的目的是回顾有关起源于中脑并投射到皮质-边缘系统和运动结构（A9和A10多巴胺通路）的多巴胺能神经元的兴奋性和功能的文献。对啮齿动物或非人灵长类动物的电生理研究表明，这些多巴胺能神经元处于静息状态或自发活动。自发活动的神经元表现出缓慢规则放电、缓慢不规则放电或快速爆发活动。在第一部分，我们将回顾神经元放电是如何被内在因素调节的，如调节冲动的树突体多巴胺自身受体、内向电压门控钠电流和钙电流与外向钾电流之间的平衡。然后，我们将回顾在调节多巴胺能细胞兴奋性方面起重要作用的主要兴奋性和抑制性通路。在第二部分，我们将讨论除了被内在和突触因素调节外，多巴胺能神经元的兴奋性如何还能被生活经历调节。多巴胺能神经元在整个发育阶段改变其放电频率，其活动可被应激性生活事件改变，并且放电模式可因急性或反复接触精神活性药物而改变。最后，这些细胞会根据行为相关刺激和学习经历改变其放电模式。我们将通过讨论多巴胺能神经元生理学的变化如何参与药物成瘾等精神疾病的发生或加重来得出结论。
