Hobin Jennifer A, Goosens Ki A, Maren Stephen
Department of Psychology and Neuroscience Program, University of Michigan, Ann Arbor, Michigan 48109-1109, USA.
J Neurosci. 2003 Sep 10;23(23):8410-6. doi: 10.1523/JNEUROSCI.23-23-08410.2003.
The context in which fear memories are extinguished has important implications for treating human fear and anxiety disorders. Extinction of Pavlovian fear conditioning is context specific; after extinction, fear responses are reduced only in the extinction context and remain elevated in every other context. Contextual modulation of spike firing in the amygdala is a putative mechanism for the context-specific expression of extinguished fear. To test this possibility, we conditioned rats to fear two auditory conditional stimuli (CSs) and then extinguished each CS in separate and distinct contexts. Thereafter, single-unit activity in the lateral nucleus of the amygdala (LA) and freezing behavior were recorded during tests in which each CS was presented in each extinction context. Hence, each CS was tested in its own extinction context and in the context of the other CS. Conditional freezing was context dependent; fear to an extinguished CS was low in its own extinction context and high in the other test context. Similarly, the majority of LA neurons exhibited context-dependent spike firing; short-latency spike firing was greater to both CSs when they were presented outside of their own extinction context. In contrast, behavioral and neuronal responses to either non-extinguished CSs or habituated auditory stimuli were not contextually modulated. Context-dependent neuronal activity in the LA may be an important mechanism for disambiguating the meaning of fear signals, thereby enabling appropriate behavioral responses to such stimuli.
恐惧记忆被消除时的情境对于治疗人类恐惧和焦虑症具有重要意义。巴甫洛夫式恐惧条件反射的消除具有情境特异性；消除后，恐惧反应仅在消除情境中降低，而在其他任何情境中仍保持较高水平。杏仁核中动作电位发放的情境调节是消除恐惧的情境特异性表达的一种推测机制。为了验证这种可能性，我们使大鼠对两种听觉条件刺激（CSs）产生恐惧，然后在单独且不同的情境中分别消除每种CS。此后，在测试过程中记录杏仁核外侧核（LA）的单单位活动和僵住行为，在测试中每种CS在各自的消除情境中呈现。因此，每种CS在其自身的消除情境以及另一种CS的情境中接受测试。条件性僵住取决于情境；对已消除的CS的恐惧在其自身的消除情境中较低，而在另一种测试情境中较高。同样，大多数LA神经元表现出与情境相关的动作电位发放；当两种CS在其自身的消除情境之外呈现时，对它们的短潜伏期动作电位发放都更强。相比之下，对未消除的CS或习惯化听觉刺激的行为和神经元反应没有受到情境调节。LA中与情境相关的神经元活动可能是区分恐惧信号含义的重要机制，从而使机体能够对这类刺激做出适当的行为反应。
