Masmudi-Martín Mariam, Navarro-Lobato Irene, López-Aranda Manuel F, Quiros-Ortega María E, Carretero-Rey Marta, Garcia-Garrido María F, López Téllez Juan F, Jiménez-Recuerda Inmaculada, Muñoz de Leon López Cristina A, Khan Zafar U
Laboratory of Neurobiology, CIMES, University of Malaga, Malaga, Spain.
Department of Medicine, Faculty of Medicine, University of Malaga, Malaga, Spain.
CNS Neurosci Ther. 2024 Apr;30(4):e14727. doi: 10.1111/cns.14727.
Ventral pathway circuits are constituted by the interconnected brain areas that are distributed throughout the brain. These brain circuits are primarily involved in processing of object related information in brain. However, their role in object recognition memory (ORM) enhancement remains unknown. Here, we have studied on the implication of these circuits in ORM enhancement and in reversal of ORM deficit in aging.
The brain areas interconnected to ventral pathway circuits in rat brain were activated by an expression of a protein called regulator of G-protein signaling 14 of 414 amino acids (RGS14). RGS14 is an ORM enhancer and therefore used here as a gain-in-function tool. ORM test and immunohistochemistry, lesions, neuronal arborization, and knockdown studies were performed to uncover the novel function of ventral pathway circuits.
An activation of each of the brain areas interconnected to ventral pathway circuits individually induced enhancement in ORM; however, same treatment in brain areas not interconnected to ventral pathway circuits produced no effect. Further study in perirhinal cortex (PRh), area V2 of visual cortex and frontal cortex (FrC), which are brain areas that have been shown to be involved in ORM and are interconnected to ventral pathway circuits, revealed that ORM enhancement seen after the activation of any one of the three brain areas was unaffected by the lesions in other two brain areas either individually in each area or even concurrently in both areas. This ORM enhancement in all three brain areas was associated to increase in structural plasticity of pyramidal neurons where more than 2-fold higher dendritic spines were observed. Additionally, we found that an activation of either PRh, area V2, or FrC not only was adequate but also was sufficient for the reversal of ORM deficit in aging rats, and the blockade of RGS14 activity led to loss in increase in dendritic spine density and failure in reversal of ORM deficit.
These results suggest that brain areas interconnected to ventral pathway circuits facilitate ORM enhancement by an increase in synaptic connectivity between the local brain area circuits and the passing by ventral pathway circuits and an upregulation in activity of ventral pathway circuits. In addition, the finding of the reversal of ORM deficit through activation of an interconnected brain area might serve as a platform for developing not only therapy against memory deficits but also strategies for other brain diseases in which neuronal circuits are compromised.
腹侧通路回路由分布于全脑的相互连接的脑区构成。这些脑回路主要参与大脑中与物体相关信息的处理。然而，它们在增强物体识别记忆（ORM）方面的作用仍不明确。在此，我们研究了这些回路在增强ORM以及逆转衰老过程中ORM缺陷方面的作用。
通过一种名为414个氨基酸的G蛋白信号调节因子14（RGS14）的蛋白质表达来激活大鼠脑中与腹侧通路回路相互连接的脑区。RGS14是一种ORM增强剂，因此在此用作功能获得工具。进行了ORM测试、免疫组织化学、损伤、神经元分支和敲低研究，以揭示腹侧通路回路的新功能。
单独激活与腹侧通路回路相互连接的每个脑区均能诱导ORM增强；然而，对与腹侧通路回路不相连的脑区进行相同处理则无效果。对内侧嗅周皮质（PRh）、视觉皮质V2区和额叶皮质（FrC）进行的进一步研究表明，这三个脑区均参与ORM且与腹侧通路回路相互连接，激活这三个脑区中的任何一个后所观察到的ORM增强不受其他两个脑区单独或同时损伤的影响。这三个脑区的ORM增强均与锥体细胞结构可塑性的增加相关，观察到树突棘增加了两倍以上。此外，我们发现激活PRh、V2区或FrC不仅足以而且能够逆转衰老大鼠的ORM缺陷，阻断RGS14活性会导致树突棘密度增加的丧失以及ORM缺陷逆转的失败。
这些结果表明，与腹侧通路回路相互连接的脑区通过增加局部脑区回路与经过的腹侧通路回路之间的突触连接以及上调腹侧通路回路的活性来促进ORM增强。此外，通过激活相互连接的脑区逆转ORM缺陷这一发现，可能不仅为开发针对记忆缺陷的治疗方法提供平台，还为开发针对神经元回路受损的其他脑部疾病的策略提供平台。
