Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, Oregon, United States of America.
PLoS One. 2011 Jan 19;6(1):e15982. doi: 10.1371/journal.pone.0015982.
A key finding in studies of the neurobiology of learning memory is that the amygdala is critically involved in Pavlovian fear conditioning. This is well established in delay-cued and contextual fear conditioning; however, surprisingly little is known of the role of the amygdala in trace conditioning. Trace fear conditioning, in which the CS and US are separated in time by a trace interval, requires the hippocampus and prefrontal cortex. It is possible that recruitment of cortical structures by trace conditioning alters the role of the amygdala compared to delay fear conditioning, where the CS and US overlap. To investigate this, we inactivated the amygdala of male C57BL/6 mice with GABA (A) agonist muscimol prior to 2-pairing trace or delay fear conditioning. Amygdala inactivation produced deficits in contextual and delay conditioning, but had no effect on trace conditioning. As controls, we demonstrate that dorsal hippocampal inactivation produced deficits in trace and contextual, but not delay fear conditioning. Further, pre- and post-training amygdala inactivation disrupted the contextual but the not cued component of trace conditioning, as did muscimol infusion prior to 1- or 4-pairing trace conditioning. These findings demonstrate that insertion of a temporal gap between the CS and US can generate amygdala-independent fear conditioning. We discuss the implications of this surprising finding for current models of the neural circuitry involved in fear conditioning.
学习记忆神经生物学研究的一个重要发现是，杏仁核在巴甫洛夫式恐惧条件反射中起着至关重要的作用。这在延迟线索和情境恐惧条件反射中得到了很好的证实；然而，令人惊讶的是，人们对杏仁核在痕迹条件反射中的作用知之甚少。在痕迹恐惧条件反射中，CS 和 US 时间上被一个痕迹间隔隔开，这需要海马体和前额叶皮层的参与。痕迹条件反射中皮质结构的招募可能会改变杏仁核的作用，与 CS 和 US 重叠的延迟恐惧条件反射相比。为了研究这一点，我们在 2 对痕迹或延迟恐惧条件反射之前，用 GABA(A) 激动剂 muscimol 使雄性 C57BL/6 小鼠的杏仁核失活。杏仁核失活导致情境和延迟条件反射缺陷，但对痕迹条件反射没有影响。作为对照，我们证明了背侧海马体失活导致了痕迹和情境条件反射的缺陷，但不导致延迟恐惧条件反射的缺陷。此外，在训练前后进行杏仁核失活会破坏情境条件反射，但不会破坏痕迹条件反射的线索成分，就像在 1 对或 4 对痕迹条件反射之前输注 muscimol 一样。这些发现表明，在 CS 和 US 之间插入时间间隔可以产生不依赖于杏仁核的恐惧条件反射。我们讨论了这一令人惊讶的发现对当前涉及恐惧条件反射的神经回路模型的意义。
