Rasopathy Program, Division of Experimental Hematology and Cancer Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, United States.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, United States.
Elife. 2023 Apr 17;12:e85064. doi: 10.7554/eLife.85064.
The mesolimbic dopamine system is an evolutionarily conserved set of brain circuits that play a role in attention, appetitive behavior, and reward processing. In this circuitry, ascending dopaminergic projections from the ventral midbrain innervate targets throughout the limbic forebrain, such as the ventral striatum/nucleus accumbens (NAc). Dopaminergic signaling in the NAc has been widely studied for its role in behavioral reinforcement, reward prediction error encoding, and motivational salience. Less well characterized is the role of dopaminergic neurotransmission in the response to surprising or alerting sensory events. To address this, we used the genetically encoded dopamine sensor dLight1 and fiber photometry to explore the ability of striatal dopamine release to encode the properties of salient sensory stimuli in mice, such as threatening looming discs. Here, we report that lateral NAc (LNAc) dopamine release encodes the rate and magnitude of environmental luminance changes rather than the visual stimulus threat level. This encoding is highly sensitive, as LNAc dopamine could be evoked by light intensities that were imperceptible to human experimenters. We also found that light-evoked dopamine responses are wavelength-dependent at low irradiances, independent of the circadian cycle, robust to previous exposure history, and involve multiple phototransduction pathways. Thus, we have further elaborated the mesolimbic dopamine system's ability to encode visual information in mice, which is likely relevant to a wide body of scientists employing light sources or optical methods in behavioral research involving rodents.
中脑边缘多巴胺系统是一组进化保守的脑回路，在注意力、欲望行为和奖励处理中发挥作用。在这个回路中，来自腹侧中脑的上升多巴胺能投射支配边缘前脑的各个靶区，如腹侧纹状体/伏隔核（NAc）。NAc 中的多巴胺信号已被广泛研究，其在行为强化、奖励预测错误编码和动机显著性方面发挥作用。多巴胺能神经传递在对令人惊讶或警示的感觉事件的反应中的作用则不太为人所知。为了解决这个问题，我们使用了基因编码的多巴胺传感器 dLight1 和光纤光度法来探索纹状体多巴胺释放在编码小鼠中显著感觉刺激（如威胁性逼近的圆盘）特性方面的能力。在这里，我们报告说，外侧 NAc（LNAc）多巴胺释放编码环境亮度变化的速率和幅度，而不是视觉刺激威胁水平。这种编码非常敏感，因为 LNAc 多巴胺可以被人类实验者无法察觉的光强度激发。我们还发现，在低辐照度下，光诱发的多巴胺反应与波长有关，与昼夜节律周期无关，对先前的暴露史具有很强的抗性，并且涉及多种光转导途径。因此，我们进一步阐述了中脑边缘多巴胺系统在小鼠中编码视觉信息的能力，这可能与广泛的科学家群体有关，他们在涉及啮齿动物的行为研究中使用光源或光学方法。
