Akirav Irit, Raizel Hagit, Maroun Mouna
Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel.
Eur J Neurosci. 2006 Feb;23(3):758-64. doi: 10.1111/j.1460-9568.2006.04603.x.
In auditory fear conditioning, repeated presentation of the tone in the absence of the shock leads to extinction of the acquired fear response. Both the infra limbic prefrontal cortex (IL) and the basolateral amygdala (BLA) are involved in extinction. In this study, we examine the involvement of these two regions in extinction by manipulating the gamma-aminobutyric acid (GABA)ergic system, in the Sprague-Dawley rat. We microinfused a low dose of the GABA(A) agonist muscimol into the IL or BLA. Muscimol infused to IL before extinction training, but not after either a short (five-trials) or long (15-trials) extinction training, resulted in long-term facilitation of extinction. Infusion of muscimol to the BLA following a short (five-trial) extinction session facilitated extinction at least 48-h post-drug infusion. The differences in the temporal parameters of the effects of muscimol in the IL or BLA, suggest differential involvement of these structures in long-term extinction of fear memory. We propose a facilitating role for GABA(A) neurotransmission in the IL in triggering the onset of fear extinction and its maintenance, whereas in the BLA, GABA(A) neurotransmission facilitates extinction consolidation. The involvement of GABA(A) receptors in fear extinction in the prefrontal cortex and amygdala is of particular interest, because of the role of these areas in emotional processes, and the role of the GABA(A) receptors in anxiety states.
在听觉恐惧条件反射中，在无电击情况下重复呈现音调会导致习得的恐惧反应消退。边缘下前额叶皮质（IL）和基底外侧杏仁核（BLA）均参与消退过程。在本研究中，我们通过操纵斯普拉格-道利大鼠的γ-氨基丁酸（GABA）能系统，研究这两个脑区在消退中的作用。我们将低剂量的GABA(A)激动剂蝇蕈醇微量注入IL或BLA。在消退训练前而非短时间（五次试验）或长时间（十五次试验）消退训练后将蝇蕈醇注入IL，会导致消退的长期促进。在短时间（五次试验）消退训练后向BLA注入蝇蕈醇，在药物注入后至少48小时促进了消退。蝇蕈醇对IL或BLA作用的时间参数差异，表明这些结构在恐惧记忆长期消退中的不同参与情况。我们提出GABA(A)神经传递在IL中对触发恐惧消退的开始及其维持起促进作用，而在BLA中，GABA(A)神经传递促进消退巩固。由于这些脑区在情绪过程中的作用以及GABA(A)受体在焦虑状态中的作用，GABA(A)受体在额叶皮质和杏仁核恐惧消退中的参与情况尤其令人关注。
