Department of Biology, University of Virginia, Charlottesville, VA 22903, USA.
Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13788-93. doi: 10.1073/pnas.1103214108. Epub 2011 Aug 1.
The ability to learn, remember, and respond to emotional events is a powerful survival strategy. However, dysregulated behavioral and physiological responses to these memories are maladaptive. To fully understand learned fear and the pathologies that arise during response malfunction we must reveal the environmental variables that influence learned fear responses. Light, a ubiquitous environmental feature, modulates cognition and anxiety. We hypothesized that light modulates responses to learned fear. Using tone-cued fear conditioning, we found that light enhances behavioral responses to learned fear in C57BL/6J mice. Mice in light freeze more in response to a conditioned cue than mice in darkness. The absence of significant freezing during a 2-wk habituation period and during intertrial intervals indicated that light specifically modulates freezing to the learned acoustic cue rather than the context of the experimental chamber. Repeating our assay in two photoreceptor mutant models, Pde6b(rd1/rd1) and Opn4(-/-) mice, revealed that light-dependent enhancement of conditioned fear is driven primarily by the rods and/or cones. By repeating our protocol with an altered lighting regimen, we found that lighting conditions acutely modulate responses when altered between conditioning and testing. This is manifested either as an enhancement of freezing when light is added during testing or as a depression of freezing when light is removed during testing. Acute enhancement, but not depression, requires both rod/cone- and melanopsin-dependent photoreception. Our results demonstrate a modulation by light of behavioral responses to learned fear.
学习、记忆和对情绪事件做出反应的能力是一种强大的生存策略。然而,对这些记忆的行为和生理反应失调是适应不良的。为了充分了解习得性恐惧以及在反应功能障碍期间出现的病理学,我们必须揭示影响习得性恐惧反应的环境变量。光作为一种普遍存在的环境特征,调节认知和焦虑。我们假设光调节对习得性恐惧的反应。通过使用音调提示的恐惧条件反射,我们发现光增强了 C57BL/6J 小鼠对习得性恐惧的行为反应。与在黑暗中的小鼠相比,在光线下的小鼠对条件性线索的冻结反应更多。在 2 周的习惯化期间和在试验间间隔期间没有明显的冻结表明,光特异性地调节对习得性声音线索的冻结,而不是调节实验室的环境。在两种光感受器突变模型(Pde6b(rd1/rd1) 和 Opn4(-/-) 小鼠)中重复我们的实验,揭示了光依赖性条件恐惧增强主要是由视杆细胞和/或视锥细胞驱动的。通过用改变的照明方案重复我们的方案,我们发现当在条件作用和测试之间改变照明条件时,光会急性调节反应。这表现为在测试期间添加光时冻结增强,或者在测试期间去除光时冻结减弱。急性增强(而非抑制)需要视杆/视锥和黑视蛋白依赖性光感受。我们的结果表明,光对学习恐惧的行为反应具有调节作用。