Overexpression of the NR2A subunit in the forebrain impairs long‐term social recognition and non‐social olfactory memory

Genes Brain and Behavior (Impact Factor: 3.66). 04/2014; 13(4):376-84. DOI: 10.1111/gbb.12123
Source: PubMed


Animals must recognize and remember conspecifics and potential mates, and distinguish these animals from potential heterospecific competitors and predators. Despite its necessity, aged animals are known to exhibit impaired social recognition memory. As the brain ages, the ratio of NR2A:NR2B in the brain increases over time and has been postulated to underlie the cognitive decline observed during the aging process. Here, we test the hypothesis that an increased NR2A:NR2B subunit ratio underlies long-term social recognition memory. Using transgenic overexpression of NR2A in the forebrain regions, we investigated the ability of these mice to learn and remember male and female conspecifics, mice of another strain and animals of another rodent species, the rat. Furthermore, due to the importance of olfaction in social recognition, we tested the olfactory memory in the NR2A transgenic mice. Our series of behavioral experiments revealed significant impairments in the NR2A transgenic mice in long-term social memory of both male and female conspecifics. Additionally, the NR2A transgenic mice are unable to recognize mice of another strain or rats. The NR2A transgenic mice also exhibited long-term memory impairments in the olfactory recognition task. Taken together, our results provide evidence that an increased NR2A:NR2B ratio in the forebrain leads to reduced long-term memory function, including the ethologically important memories such as social recognition and olfactory memory.

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    • "So far, similar increase was demonstrated after noncontingent cocaine administration in rats (Ary and Szumlinski 2007) and such overexpression of GluN2A subunit finding may suggest that the NMDA receptor kinetics of currents deactivation are faster than in controls (Yashiro and Philpot 2008). Such changes may also be associated with memory impairment (Jacobs and Tsien 2014) or enhanced cue and contextual fear conditioning (Gilmartin et al. 2013). "
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