A Hippocampal NR2B Deficit Can Mimic Age-Related Changes in Long-Term Potentiation and Spatial Learning in the Fischer 344 Rat

• Published in: The Journal of neuroscience Vol. 22; no. 9; pp. 3628 - 3637
• Main Authors: Clayton, Daniel A, Mesches, Michael H, Alvarez, Enriquez, Bickford, Paula C, Browning, Michael D
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 01-05-2002; Society for Neuroscience
• Subjects: Action Potentials - physiology; Aging - metabolism; Animals; Behavior, Animal - drug effects; Blotting, Western; Calcium Channel Blockers - pharmacology; Catheterization; Electric Stimulation; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Gene Expression - drug effects; Hippocampus - drug effects; Hippocampus - metabolism; In Vitro Techniques; Kynurenic Acid - analogs & derivatives; Kynurenic Acid - pharmacology; Long-Term Potentiation - drug effects; Long-Term Potentiation - physiology; Male; Maze Learning - drug effects; Maze Learning - physiology; Microinjections; Oligonucleotides, Antisense - administration & dosage; Oligonucleotides, Antisense - pharmacology; Rats; Rats, Inbred F344; Receptors, N-Methyl-D-Aspartate - deficiency; Receptors, N-Methyl-D-Aspartate - genetics; Receptors, N-Methyl-D-Aspartate - metabolism; Spermine - pharmacology
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.22-09-03628.2002

Aged rats are known to have deficits in spatial learning behavior in the Morris water maze. We have found that aged rats also have deficits in NR2B protein expression and that the protein expression deficit is correlated with their performance in the Morris water maze. To test whether this NR2B deficit was sufficient to account for the behavioral deficit, we used antisense oligonucleotides to specifically knock down NR2B subunit expression in the hippocampus of young rats. NR2B antisense treatment diminished NMDA receptor responses, abolished NMDA-dependent long-term potentiation (LTP), and impaired spatial learning. These data demonstrate the important role of NR2B in LTP and learning and memory and suggest a role for reduced NR2B expression in age-related cognitive decline.