Center for the Neurobiology of Addiction, Pain, and Emotion, Department of Anesthesiology and Pain Medicine, Department of Pharmacology, University of Washington, 98195, Seattle, WA, USA.
Center for the Neurobiology of Addiction, Pain, and Emotion, Department of Anesthesiology and Pain Medicine, Department of Pharmacology, University of Washington, 98195, Seattle, WA, USA.
Neuropharmacology. 2021 Oct 15;198:108725. doi: 10.1016/j.neuropharm.2021.108725. Epub 2021 Aug 8.
Reinforcement, reward, and aversion are fundamental processes for guiding appropriate behaviors. Longstanding theories have pointed to dopaminergic neurons of the ventral tegmental area (VTA) and the limbic systems' descending pathways as crucial systems for modulating these behaviors. The application of optogenetic techniques in neurotransmitter- and projection-specific circuits has supported and enhanced many preexisting theories but has also revealed many unexpected results. Here, we review the past decade of optogenetic experiments to study the neural circuitry of reinforcement and reward/aversion with a focus on the mesolimbic dopamine system and brain areas along the medial forebrain bundle (MFB). The cumulation of these studies to date has revealed generalizable findings across molecularly defined cell types in areas of the basal forebrain and anterior hypothalamus. Optogenetic stimulation of GABAergic neurons in these brain regions drives reward and can support positive reinforcement and optogenetic stimulation of glutamatergic neurons in these regions drives aversion. We also review studies of the activity dynamics of neurotransmitter defined populations in these areas which have revealed varied response patterns associated with motivated behaviors. This article is part of the special Issue on 'Neurocircuitry Modulating Drug and Alcohol Abuse'.
强化、奖励和厌恶是指导适当行为的基本过程。长期以来的理论指出，腹侧被盖区（VTA）的多巴胺能神经元和边缘系统的下行通路是调节这些行为的关键系统。光遗传学技术在神经递质和投射特异性回路中的应用支持和增强了许多现有理论，但也揭示了许多意外的结果。在这里，我们回顾了过去十年中使用光遗传学实验来研究强化和奖励/厌恶的神经回路的研究，重点是中脑边缘多巴胺系统和沿内侧前脑束（MFB）的脑区。迄今为止，这些研究的积累揭示了在基底前脑和前下丘脑的分子定义细胞类型中具有普遍性的发现。这些脑区中 GABA 能神经元的光遗传学刺激驱动奖励，并能支持正强化，而这些区域中谷氨酸能神经元的光遗传学刺激则驱动厌恶。我们还回顾了这些区域中神经递质定义群体的活动动力学研究，这些研究揭示了与动机行为相关的各种反应模式。本文是“调节药物和酒精滥用的神经回路”特刊的一部分。
