Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, South Carolina, USA.
J Comp Neurol. 2021 Jul 1;529(10):2450-2463. doi: 10.1002/cne.25104. Epub 2021 Jan 14.
The basolateral nuclear complex (BNC) of the amygdala plays an important role in the generation of emotional/motivational behavior and the consolidation of emotional memories. Activation of M1 cholinergic receptors (M1Rs) in the BNC is critical for memory consolidation. Previous receptor binding studies in the monkey amygdala demonstrated that the BNC has a high density of M1Rs, but did not have sufficient resolution to identify which neurons in the BNC expressed them. This was accomplished in the present immunohistochemical investigation using an antibody for the m1 receptor (m1R). Analysis of m1Rs in the monkey BNC using immunoperoxidase techniques revealed that their expression was very dense in the BNC, and suggested that virtually all of the pyramidal projection neurons (PNs) in all of the BNC nuclei were m1R-immunoreactive (m1R+). This was confirmed with dual-labeling immunofluorescence using staining for calcium/calmodulin-dependent protein kinase II (CaMK) as a marker for BNC PNs. However, additional dual-labeling studies indicated that one-third of inhibitory interneurons (INs) expressing glutamic acid decarboxylase (GAD) were also m1R+. Moreover, the finding that 60% of parvalbumin (PV) immunoreactive neurons were m1R+ indicated that this IN subpopulation was the main GAD+ subpopulation exhibiting m1R expression. The cholinergic innervation of the amygdala is greatly reduced in Alzheimer's disease and there is currently considerable interest in developing selective M1R positive allosteric modulators (PAMs) to treat the symptoms. The results of the present study indicate that M1Rs in both PNs and INs in the primate BNC would be targeted by M1R PAMs.
杏仁核基底外侧核团（BNC）在产生情绪/动机行为和情绪记忆的巩固中起着重要作用。BNC 中 M1 胆碱能受体（M1R）的激活对于记忆巩固至关重要。以前在猴子杏仁核中的受体结合研究表明，BNC 具有高密度的 M1R，但分辨率不足以确定 BNC 中的哪些神经元表达它们。在本研究中，使用针对 m1 受体（m1R）的抗体完成了这项免疫组织化学研究。使用免疫过氧化物酶技术分析猴子 BNC 中的 m1R 表明，它们在 BNC 中的表达非常密集，并表明 BNC 中的几乎所有锥体投射神经元（PN）都是 m1R-免疫反应性的（m1R+）。使用钙/钙调蛋白依赖性蛋白激酶 II（CaMK）作为 BNC PN 的标志物进行双重标记免疫荧光染色证实了这一点。然而，进一步的双重标记研究表明，三分之一表达谷氨酸脱羧酶（GAD）的抑制性中间神经元（IN）也是 m1R+。此外，发现 60%的囊泡蛋白（PV）免疫反应性神经元是 m1R+，表明该 IN 亚群是主要的 GAD+亚群，表现出 m1R 表达。阿尔茨海默病患者的杏仁核胆碱能神经支配大大减少，目前人们对开发选择性 M1R 正变构调节剂（PAMs）来治疗该疾病的症状产生了浓厚的兴趣。本研究的结果表明，灵长类动物 BNC 中的 PN 和 IN 中的 M1R 都会成为 M1R PAMs 的靶点。
