Masmudi-Martín Mariam, Navarro-Lobato Irene, López-Aranda Manuel F, Browning Philip G F, Simón Ana-María, López-Téllez Juan F, Jiménez-Recuerda Inmaculada, Martín-Montañez Elisa, Pérez-Mediavilla Alberto, Frechilla Diana, Baxter Mark G, Khan Zafar U
Laboratory of Neurobiology, CIMES, University of Malaga, Campus Teatinos s/n, 29071 Malaga, Spain; Department of Medicine, Faculty of Medicine, University of Malaga, Campus Teatinos s/n, 29071 Malaga, Spain.
Department of Neuroscience, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1065, New York, NY 10029, United States.
Neuroscience. 2020 Nov 10;448:287-298. doi: 10.1016/j.neuroscience.2020.08.039. Epub 2020 Sep 6.
The integrity of the perirhinal cortex (PRh) is essential for object recognition memory (ORM) function, and damage to this brain area in animals and humans induces irreversible ORM deficits. Here, we show that activation of area V2, a brain area interconnected with brain circuits of ventral stream and medial temporal lobe that sustain ORM, by expression of regulator of G-protein signaling 14 of 414 amino acids (RGS14) restored ORM in memory-deficient PRh-lesioned rats and nonhuman primates. Furthermore, this treatment was sufficient for full recovery of ORM in rodent models of aging and Alzheimer's disease, conditions thought to affect multiple brain areas. Thus, RGS14-mediated activation of area V2 has therapeutic relevance in the recovery of recognition memory, a type of memory that is primarily affected in patients or individuals with symptoms of memory dysfunction. These findings suggest that area V2 modulates the processing of memory-related information through activation of interconnected brain circuits formed by the participation of distinct brain areas.
鼻周皮质(PRh)的完整性对于物体识别记忆(ORM)功能至关重要,动物和人类中该脑区受损会导致不可逆的ORM缺陷。在此,我们表明,通过表达414个氨基酸的G蛋白信号调节因子14(RGS14)来激活V2区(一个与维持ORM的腹侧流和内侧颞叶脑回路相互连接的脑区),可恢复记忆缺陷的PRh损伤大鼠和非人灵长类动物的ORM。此外,这种治疗足以使衰老和阿尔茨海默病啮齿动物模型中的ORM完全恢复,而这些疾病被认为会影响多个脑区。因此,RGS14介导的V2区激活在识别记忆恢复中具有治疗意义,识别记忆是一种在有记忆功能障碍症状的患者或个体中主要受到影响的记忆类型。这些发现表明,V2区通过激活由不同脑区参与形成的相互连接的脑回路来调节与记忆相关信息的处理。