title: Increased NR2A:NR2B ratio compresses long-term depression range and constrains long-term memory.
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 100 Hz-induced long-term potentiation (LTP) in the CA1 region of the hippocampus, but selectively abolished LTD responses in the 3-5 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.
authors.affiliation: Brain and Behavior Discovery Institute and Department of Neurology, Medical College of Georgia, Georgia Health Sciences University, Augusta, GA 30907, USA.
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Cui
authors.forename: Ruiben
authors.initials: R
authors.lastname: Feng
authors.forename: Stephanie
authors.initials: S
authors.lastname: Jacobs
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Duan
authors.forename: Huimin
authors.initials: H
authors.lastname: Wang
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Cao
authors.forename: Joe Z
authors.initials: JZ
authors.lastname: Tsien
mesh_terms: D000818:Animals; D003863:Depression; D005239:Fear; D006624:Hippocampus / Q000502:physiology; D018782:Maze Learning; D057567:Memory, Long-Term / Q000502:physiology*; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
chemical_list: C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate