Increased NR2A:NR2B ratio compresses long-term depression range and constrains long-term memory

Zhenzhong Cui, Ruiben Feng, Stephanie Jacobs, Yanhong Duan, Huimin Wang, Xiaohua Cao, Joe Z. Tsien

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

The NR2A:NR2B subunit ratio of the NMDA receptors is widely known to increase in the brain from postnatal development to sexual maturity and to aging, yet its impact on memory function remains speculative. We have generated forebrain-specific NR2A overexpression transgenic mice and show that these mice had normal basic behaviors and short-term memory, but exhibited broad long-term memory deficits as revealed by several behavioral paradigms. Surprisingly, increased NR2A expression did not affect 1-Hz-induced long-term depression (LTD) or 100â.Hz-induced long-term potentiation (LTP) in the CA1 region of the hippocampus, but selectively abolished LTD responses in the 3-5â.Hz frequency range. Our results demonstrate that the increased NR2A:NR2B ratio is a critical genetic factor in constraining long-term memory in the adult brain. We postulate that LTD-like process underlies post-learning information sculpting, a novel and essential consolidation step in transforming new information into long-term memory.

Original languageEnglish (US)
Article number1036
JournalScientific reports
Volume3
DOIs
StatePublished - Jan 28 2013

ASJC Scopus subject areas

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    Cui, Z., Feng, R., Jacobs, S., Duan, Y., Wang, H., Cao, X., & Tsien, J. Z. (2013). Increased NR2A:NR2B ratio compresses long-term depression range and constrains long-term memory. Scientific reports, 3, [1036]. https://doi.org/10.1038/srep01036