Department of Neuroscience, Columbia University, New York, NY, USA.
Ann Med. 2010 Mar;42(2):115-22. doi: 10.3109/07853890903583666.
Learned safety is established by negatively correlating the occurrence of a neutral stimulus and a noxious stimulus, which renders the previously neutral stimulus a 'safety signal'. While the neurophysiological and molecular mechanisms have been characterized in mice, it is currently not known how the neural substrates involved compare between mice and people.
Here we attempt to adapt the original animal protocol to humans and use functional magnetic resonance imaging to examine neural responses to the conditioned stimulus in safety conditioned and fear conditioned subjects. Diffusion tensor imaging (DTI) was used in a parallel group of subjects as a first approach to delineate the underlying neural circuitry.
Learned safety is associated with dampened amygdala and increased dorsolateral prefrontal cortex and caudate responses and paralleled by pupillary constriction. A neural connection between the amygdala and the dorsolateral prefrontal cortex is suggested by DTI.
We present a translational bridge between mouse and human models of learned safety in which cellular and molecular insights from animal experiments are extended to the human neural circuitry. This study provides an example of how animal experiments can be used to inform and target human studies, which in turn can corroborate results obtained in experimental animals.
学习型安全是通过将中性刺激与有害刺激的发生呈负相关来建立的，这使得之前的中性刺激成为“安全信号”。虽然已经在小鼠中描述了神经生理学和分子机制，但目前尚不清楚涉及的神经基质在小鼠和人类之间有何不同。
在这里，我们试图将原始的动物方案适应于人类，并使用功能磁共振成像来检查安全条件和恐惧条件下的受试者对条件刺激的神经反应。在并行组的受试者中使用弥散张量成像 (DTI) 作为描绘潜在神经回路的初步方法。
学习型安全与杏仁核反应减弱和背外侧前额叶皮层和尾状核反应增强以及瞳孔收缩有关。DTI 提示杏仁核和背外侧前额叶皮层之间存在神经连接。
我们在学习型安全的小鼠和人类模型之间架起了一座转化桥梁，其中动物实验的细胞和分子见解扩展到了人类的神经回路。这项研究提供了一个范例，说明如何利用动物实验为人类研究提供信息和目标，而人类研究反过来又可以证实实验动物中获得的结果。
