Giachero Marcelo, Calfa Gaston D, Molina Victor A
IFEC-CONICET, Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Hippocampus. 2015 May;25(5):545-55. doi: 10.1002/hipo.22409. Epub 2015 Jan 20.
GABAergic signaling in the basolateral amygdala complex (BLA) plays a crucial role on the modulation of the stress influence on fear memory. Moreover, accumulating evidence suggests that the dorsal hippocampus (DH) is a downstream target of BLA neurons in contextual fear. Given that hippocampal structural plasticity is proposed to provide a substrate for the storage of long-term memories, the main aim of this study is to evaluate the modulation of GABA neurotransmission in the BLA on spine density in the DH following stress on contextual fear learning. The present findings show that prior stressful experience promoted contextual fear memory and enhanced spine density in the DH. Intra-BLA infusion of midazolam, a positive modulator of GABAa sites, prevented the facilitating influence of stress on both fear retention and hippocampal dendritic spine remodeling. Similarly to the stress-induced effects, the blockade of GABAa sites within the BLA ameliorated fear memory emergence and induced structural remodeling in the DH. These findings suggest that GABAergic transmission in BLA modulates the structural changes in DH associated to the influence of stress on fear memory.
基底外侧杏仁核复合体(BLA)中的γ-氨基丁酸能信号传导在调节应激对恐惧记忆的影响方面起着至关重要的作用。此外,越来越多的证据表明,在情境恐惧中,背侧海马体(DH)是BLA神经元的下游靶点。鉴于海马体结构可塑性被认为是长期记忆存储的基础,本研究的主要目的是评估应激对情境恐惧学习后,BLA中γ-氨基丁酸神经传递对DH中脊柱密度的调节作用。目前的研究结果表明,先前的应激经历促进了情境恐惧记忆,并增加了DH中的脊柱密度。向BLA内注射咪达唑仑(一种GABAA位点的正向调节剂)可防止应激对恐惧记忆保留和海马体树突棘重塑的促进作用。与应激诱导的效应类似,阻断BLA内的GABAA位点可改善恐惧记忆的出现,并在DH中诱导结构重塑。这些发现表明,BLA中的γ-氨基丁酸能传递调节了与应激对恐惧记忆影响相关的DH结构变化。