Signaling through cGMP-Dependent Protein Kinase I in the Amygdala Is Critical for Auditory-Cued Fear Memory and Long-Term Potentiation
Signaling through cGMP-Dependent Protein Kinase I in the Amygdala Is Critical for Auditory-Cued Fear Memory and Long-Term Potentiation
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DOI：
10.1523/jneurosci.2216-08.2008
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发表时间：
2008-12-24
影响因子：
5.3
通讯作者：
Kleppisch, Thomas
中科院分区：
文献类型：
--
作者：
Paul, Cindy;Schoeberl, Florian;Kleppisch, Thomas
长期增强（LTP）将感觉信息从皮质和丘脑神经元传递到外侧杏仁核（LA）的主要神经元，被认为是联想恐惧学习的细胞机制。一氧化氮（NO）是一种广泛参与突触可塑性和行为的信使分子，已被证明可以增强LA的LTP以及联想恐惧记忆的巩固。其他证据表明，no诱导的LTP和杏仁核依赖性学习的增强需要通过可溶性关酰环化酶（sGC）和cgmp依赖性蛋白激酶（cGK）发出信号。哺乳动物具有两个cGK基因：prkg1基因产生cGKI型亚型，cGKI α和cGKI β， prkg2基因编码cGK II型。据报道，cGKI和cGKII都在杏仁核中表达，cGKII参与控制焦虑样行为。由于缺乏针对单个cGK亚型的选择性药理学工具，我们使用不同的敲除小鼠模型来检测cGKI和cGKII在LA和巴甫洛夫恐惧条件反射中对LTP的功能。我们发现cGKI特异性地在LA中以cGKI β为主要亚型表达。我们进一步发现，在cgki缺陷突变体中，丘脑和皮层输入到LA的LTP都显著减少，并且听觉提示的恐惧记忆选择性受损。相比之下，cGKII无突变体缺乏这些表型。我们的数据表明，cGKI的功能，可能是β亚型，在LA中，支持突触可塑性和恐惧记忆的巩固。
Long-term potentiation (LTP) of inputs relaying sensory information from cortical and thalamic neurons to principal neurons in the lateral amygdala (LA) is thought to serve as a cellular mechanism for associative fear learning. Nitric oxide (NO), a messenger molecule widely implicated in synaptic plasticity and behavior, has been shown to enhance LTP in the LA as well as consolidation of associative fear memory. Additional evidence suggests that NO-induced enhancement of LTP and amygdala-dependent learning requires signaling through soluble guanylyl cyclase (sGC) and cGMP-dependent protein kinase (cGK). Mammals possess two genes for cGK: the prkg1 gene gives rise to the cGK type I isoforms, cGKI alpha and cGKI beta, and the prkg2 gene encodes the cGK type II. Reportedly, both cGKI and cGKII are expressed in the amygdala, and cGKII is involved in controlling anxiety-like behavior. Because selective pharmacological tools for individual cGK isoforms are lacking, we used different knock-out mouse models to examine the function of cGKI and cGKII for LTP in the LA and pavlovian fear conditioning. We found robust expression of the cGKI specifically in the LA with cGKI beta as the prevailing isoform. We further show a marked reduction of LTP at both thalamic and cortical inputs to the LA and a selective impairment of auditory-cued fearmemoryin cGKI-deficient mutants. In contrast, cGKII null mutants lack these phenotypes. Our data suggest a function of cGKI, likely the beta isoform, in the LA, supporting synaptic plasticity and consolidation of fear memory.