Short-Term Adaptation of Conditioned Fear Responses Through Endocannabinoid Signaling in the Central Amygdala
Short-Term Adaptation of Conditioned Fear Responses Through Endocannabinoid Signaling in the Central Amygdala
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DOI：
10.1038/npp.2010.196
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发表时间：
2011-02-01
影响因子：
7.6
通讯作者：
Pape, Hans-Christian
中科院分区：
文献类型：
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作者：
Kamprath, Kornelia;Romo-Parra, Hector;Pape, Hans-Christian
已知大麻素受体1型（CB 1）和杏仁核（CeA）在恐惧和焦虑的处理中起着至关重要的作用，因此它们似乎特别参与恐惧状态的控制。然而，与包括杏仁核皮质亚区在内的许多其他大脑区域相比，CeA中CB 1的存在仍然是个谜。在这项研究中，我们表明，CB 1在小鼠的CeA中表达，并且在CeA中的CB 1介导短期突触可塑性，即去极化诱导的兴奋抑制（DSE）和抑制（DSI）。此外，CB 1拮抗剂AM 251增加兴奋性和抑制性突触后反应在CeA神经元。局部应用AM 251在CeA在体内导致了急剧增加的恐惧反应的听觉恐惧条件反射的范例。在杏仁核（BLA）的基底外侧核（BLA）在其他相同的协议应用AM 251后，没有检测到这样的急性行为效应，但CB 1阻断导致增加的恐惧反应，在随后的日子里，在音调曝光。此外，我们观察到DSE和DSI在CeA中的功效在恐惧条件反射后的第二天增加，这表明单个音调-休克配对导致CeA中内源性大麻素信号传导的变化。综上所述，我们的数据表明，CB 1蛋白在CeA中的存在，以及它们在确保对恐惧事件的反应的短期适应方面的关键作用，从而提出了一个潜在的治疗靶点，以伴随基于习惯的创伤后症状治疗。Neuropsychopharmacology（2011）36，652-663; doi：10.1038/npp.2010.196; 2010年10月27日在线发表
The cannabinoid receptor type 1 (CB1) and the central nucleus of the amygdala (CeA) are both known to have crucial roles in the processing of fear and anxiety, whereby they appear to be especially involved in the control of fear states. However, in contrast to many other brain regions including the cortical subregions of the amygdala, the existence of CB1 in the CeA remains enigmatic. In this study we show that CB1 is expressed in the CeA of mice and that CB1 in the CeA mediates short-term synaptic plasticity, namely depolarization-induced suppression of excitation (DSE) and inhibition (DSI). Moreover, the CB1 antagonist AM251 increased both excitatory and inhibitory postsynaptic responses in CeA neurons. Local application of AM251 in the CeA in vivo resulted in an acutely increased fear response in an auditory fear conditioning paradigm. Upon application of AM251 in the basolateral nucleus of the amygdala (BLA) in an otherwise identical protocol, no such acute behavioral effects were detected, but CB1 blockade resulted in increased fear responses during tone exposures on the subsequent days. Moreover, we observed that the efficacy of DSE and DSI in the CeA was increased on the day following fear conditioning, indicating that a single tone-shock pairing resulted in changes in endocannabinoid signaling in the CeA. Taken together, our data show the existence of CB1 proteins in the CeA, and their critical role for ensuring short-term adaptation of responses to fearful events, thereby suggesting a potential therapeutic target to accompany habituation-based therapies of post-traumatic symptoms. Neuropsychopharmacology (2011) 36, 652-663; doi:10.1038/npp.2010.196; published online 27 October 2010