McDonald Alexander Joseph, Mascagni Franco
Department of Pharmacology, Physiology, and Neuroscience, University of South Carolina School of Medicine, Columbia, South Carolina 29208, USA.
J Comp Neurol. 2004 May 17;473(1):137-46. doi: 10.1002/cne.20101.
The basolateral amygdala (ABL) is essential for the amnestic effects of benzodiazepines in aversive learning tasks. Because the alpha1 subunit of the gamma-aminobutyric acid (GABA)(A) receptor is critical for these amnestic actions, knowledge of the neuronal localization of this subunit in the ABL should contribute to an understanding of the candidate neuronal mechanisms involved. To examine this question, we used dual-labeling immunohistochemical techniques to study the localization of the alpha1 subunit in the ABL. Our results suggest that the alpha1 subunit of the GABA(A) receptor is localized primarily in GABAergic interneurons in the ABL at the somal level, although the intense neuropil staining in the lateral nucleus suggests that distal dendrites of pyramidal projection neurons in this nucleus may also contain high levels of the alpha1 subunit. The great majority of alpha1-immunoreactive interneurons also exhibit immunoreactivity for the beta2/3 subunits of the GABA(A) receptor. Parvalbumin-positive (PV+) interneurons are the main interneuronal subpopulation exhibiting alpha1 immunoreactivity, but some calretinin-positive interneurons also express this subunit. These data suggest that certain subpopulations of GABAergic interneurons in the ABL, especially PV+ cells, receive a robust GABAergic innervation. Because the most likely source of this innervation is intrinsic, these results suggest that PV+ interneurons could constitute an important component of interneuronal networks in the ABL. These networks may be critical for the generation of synchronized rhythmic oscillations involved in consolidation of emotional memories. The activation of alpha1-containing GABA(A) receptors in the ABL by benzodiazepines may disrupt rhythmic oscillations critical for memory consolidation.
基底外侧杏仁核(ABL)对于苯二氮䓬类药物在厌恶学习任务中的遗忘作用至关重要。由于γ-氨基丁酸(GABA)(A)受体的α1亚基对这些遗忘作用至关重要,了解该亚基在ABL中的神经元定位应有助于理解相关的候选神经元机制。为了研究这个问题,我们使用双标记免疫组织化学技术来研究α1亚基在ABL中的定位。我们的结果表明,GABA(A)受体的α1亚基主要定位于ABL中胞体水平的GABA能中间神经元,尽管外侧核中强烈的神经毡染色表明该核中锥体投射神经元的远端树突也可能含有高水平的α1亚基。绝大多数α1免疫反应性中间神经元也对GABA(A)受体的β2/3亚基表现出免疫反应性。小白蛋白阳性(PV+)中间神经元是表现出α1免疫反应性的主要中间神经元亚群,但一些钙视网膜蛋白阳性中间神经元也表达该亚基。这些数据表明,ABL中某些GABA能中间神经元亚群,尤其是PV+细胞,接受强大的GABA能神经支配。由于这种神经支配最可能的来源是内在的,这些结果表明PV+中间神经元可能构成ABL中神经元网络的重要组成部分。这些网络可能对参与情绪记忆巩固的同步节律振荡的产生至关重要。苯二氮䓬类药物激活ABL中含α1的GABA(A)受体可能会破坏对记忆巩固至关重要的节律振荡。