Reversal of Object Recognition Memory Deficit in Perirhinal Cortex-Lesioned Rats and Primates and in Rodent Models of Aging and Alzheimer’s Diseases

• Published in: Neuroscience Vol. 448; pp. 287 - 298
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 10.11.2020
• Subjects: Aging; Alzheimer Disease; Animals; brain memory circuit activation; Humans; lesions in perirhinal cortex; memory deficits; Memory Disorders; Perirhinal Cortex; Primates; Rats; recovery of memory dysfunctions; regulator of G protein signaling; RGS Proteins; Rodentia; memory deficits; brain memory circuit activation; RGS14414; lesions in perirhinal cortex; regulator of G protein signaling; PRh; recovery of memory dysfunctions; ORM
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2020.08.039

•RGS14414 protein expression in area V2 of rat brain induces robust enhancement in object recognition memory (ORM).•RGS14414 treatment in area V2 rescues ORM deficit induced by the perirhinal cortex lesions in rats.•RGS14414 treatment in area V2 (foveal V2) rescues ORM deficit induced by the perirhinal cortex lesions in Rhesus monkeys.•RGS14414 treatment in area V2 restores ORM in memory deficient aging rats and Alzheimer’s disease mice. 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 (RGS14414) 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, RGS14414-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.