Identification of a signaling network in lateral nucleus of amygdala important for inhibiting memory specifically related to learned fear
Identification of a signaling network in lateral nucleus of amygdala important for inhibiting memory specifically related to learned fear
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DOI：
10.1016/s0092-8674(02)01116-9
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发表时间：
2002-12-13
期刊：
影响因子：
64.5
通讯作者：
Bolshakov, VY
中科院分区：
文献类型：
--
作者：
Shumyatsky, GP;Tsvetkov, E;Bolshakov, VY
我们发现，编码胃泌素释放肽的Grp基因在杏仁核的外侧核和向外侧核传递恐惧听觉信息的区域都有高度表达。杏仁核是巴甫洛夫习得性恐惧的关联形成的核团。此外，我们发现GRP受体（GRPR）表达于外侧核的GABA能中间神经元。GRP兴奋这些中间神经元并增加它们对主神经元的抑制。GRPR缺陷小鼠表现出减少抑制的主要神经元的中间神经元，增强长时程增强（LTP），更大和更持久的长期恐惧记忆。相比之下，这些小鼠在海马区依赖的Morris迷宫中表现正常。这些实验提供了遗传学证据，证明GRP及其神经回路作为负反馈调节恐惧，并建立了Grpr基因表达，LTP和杏仁核依赖的恐惧记忆之间的因果关系。
We identified the Grp gene, encoding gastrin-releasing peptide, as being highly expressed both in the lateral nucleus of the amygdala, the nucleus where associations for Pavlovian learned fear are formed, and in the regions that convey fearful auditory information to the lateral nucleus. Moreover, we found that GRP receptor (GRPR) is expressed in GABAergic interneurons of the lateral nucleus. GRP excites these interneurons and increases their inhibition of principal neurons. GRPR-deficient mice showed decreased inhibition of principal neurons by the interneurons, enhanced long-term potentiation (LTP), and greater and more persistent long-term fear memory. By contrast, these mice performed normally in hippocampus-dependent Morris maze. These experiments provide genetic evidence that GRP and its neural circuitry operate as a negative feedback regulating fear and establish a causal relationship between Grpr gene expression, LTP, and amygdala-dependent memory for fear.