Abstract
AbstractThe expression of NMDA receptor subunit NR3A is high in the neonatal brain but low in adults. However, its functional role in the adult brain is obscure. Using wild-type (WT) and NR3A knockout (KO) mice, we show here that NR3A plays imperative roles in multiple behavioral functions in adults. NR3A deletion produced a slow locomotor phenotype with enhanced memory capacities. Hippocampal slices from juvenile and adult NR3A KO mice showed greater long-term potentiation (LTP) compared to WT slices. NR3A deletion resulted in increased expression and phosphorylation of calmodulin-dependent kinase II (CaMKII). CaMKII inhibition abrogated the enhanced LTP in NR3A KO slices. NR3A KO mice were also more sensitive to acute and chronic pain. These data reveal for the first time that NR3A, despite its low expression, plays several critical roles in behavioral activities in adults and may be a therapeutic target for modulating behaviors under normal and pathological conditions.
Highlights
Opposite to previous observations and assumptions, here we demonstrate for the first time that markedly significant differences in locomotor functions, learning and memory, and pain sensation can be detected between adult WT and NR3A KO mice
These findings indicate that the NR3A subunit, despite its relatively low expression, has a surprising imperative functional role in adult animals and might be a target for therapeutic interventions
We evaluated the expression levels of major ionotropic glutamate receptor subunits in NR3A KO mice
Summary
Animals: Animal handling and all experiments were approved by the Institutional. Animal Care and Use Committee (IACUC) at Emory University. The NR3A KO mice and WT counterparts were provided by Nobuki Nakanishi and Stuart A. Lipton at Sanford-Burnham Medical Research Institute (La Jolla, California, USA) [10]. Genotyping: DNA for genotyping was extracted from tail snips. Two separate sets of primers were used for the NR3A KO and WT mice. For the WT reaction, forward primer: 5’-CCACGGTGAGCTTGGGGAAG-3’ and reverse primer 5’-
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
