Extracellular hippocampal acetylcholine level controls amygdala function and promotes adaptive conditioned emotional response
Extracellular hippocampal acetylcholine level controls amygdala function and promotes adaptive conditioned emotional response
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DOI：
10.1523/jneurosci.3713-06.2006
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发表时间：
2006-12-27
影响因子：
5.3
通讯作者：
Desmedt, Aline
中科院分区：
文献类型：
--
作者：
Calandreau, Ludovic;Trifilieff, Pierre;Desmedt, Aline
大量数据表明，音调和情境恐惧条件反射对杏仁核和海马体的要求不同。然而，在环境刺激（离散语气与环境）中，对那些最能预测厌恶事件的刺激进行适应性选择的机制仍然难以捉摸。由于海马胆碱能神经传递被认为在不同记忆系统之间的协调中起着关键作用，从而导致适当的行为策略的选择，我们假设这种胆碱能信号可能控制杏仁核介导的音调和情境条件反射的竞争性获得。在小鼠中使用巴普洛夫恐惧条件反射，我们首先显示了在情境比离散的音调刺激更能预测的条件下，海马乙酰胆碱释放水平更高，并且在外侧（LA）和基底外侧（BLA）杏仁核内细胞外信号调节激酶1/2 （ERK1/2）激活的特定模式。其次，我们证明了海马胆碱能神经传递水平与杏仁核ERK1/2激活模式有因果关系，并实际上决定了在环境或简单音调中选择最能预测厌恶事件的刺激。具体而言，海马胆碱能信号的减少不仅损害了情境条件反射，而且在行为结果和LA/BLA ERK1/2激活模式方面也损害了对离散音调的模仿条件反射。相反，增加这种胆碱能信号不仅会破坏音调条件反射，还会促进情境恐惧条件反射。因此，这些发现强调海马胆碱能神经传递控制杏仁核功能，从而导致相关情绪信息的选择。
Ample data indicate that tone and contextual fear conditioning differentially require the amygdala and the hippocampus. However, mechanisms subserving the adaptive selection among environmental stimuli ( discrete tone vs context) of those that best predict an aversive event are still elusive. Because the hippocampal cholinergic neurotransmission is thought to play a critical role in the coordination between different memory systems leading to the selection of appropriate behavioral strategies, we hypothesized that this cholinergic signal may control the competing acquisition of amygdala-mediated tone and contextual conditioning. Using pavlovian fear conditioning in mice, we first show a higher level of hippocampal acetylcholine release and a specific pattern of extracellular signal-regulated kinase 1/2 (ERK1/2) activation within the lateral (LA) and basolateral (BLA) amygdala under conditions in which the context is a better predictor than a discrete tone stimulus. Second, we demonstrate that levels of hippocampal cholinergic neurotransmission are causally related to the patterns of ERK1/2 activation in amygdala nuclei and actually determine the selection among the context or the simple tone the stimulus that best predicts the aversive event. Specifically, decreasing the hippocampal cholinergic signal not only impaired contextual conditioning but also mimicked conditioning to the discrete tone, both in terms of the behavioral outcome and the LA/BLA ERK1/2 activation pattern. Conversely, increasing this cholinergic signal not only disrupted tone conditioning but also promoted contextual fear conditioning. Hence, these findings highlight that hippocampal cholinergic neurotransmission controls amygdala function, thereby leading to the selection of relevant emotional information.