A hippocampal NR2B deficit can mimic age-related changes in long-term potentiation and spatial learning in the Fischer 344 rat.
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.
Clayton
Daniel A
DA
Medical Scientist Training Program, Neuroscience Program, and Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Mesches
Michael H
MH
Alvarez
Enriquez
E
Bickford
Paula C
PC
Browning
Michael D
MD
D000200:Action Potentials / Q000502:physiology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002404:Catheterization; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D016194:Receptors, N-Methyl-D-Aspartate / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D013096:Spermine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D016376:Oligonucleotides, Antisense; D016194:Receptors, N-Methyl-D-Aspartate; D013096:Spermine; D007736:Kynurenic Acid; C057013:7-chlorokynurenic acid