Glutamate receptor-mediated restoration of experience-dependent place field expansion plasticity in aged rats.
Place fields of hippocampal pyramidal cells expand asymmetrically when adult rats repeatedly follow the same route. This behaviorally induced expression of neuronal plasticity uses an NMDAR-dependent, LTP-like mechanism and could be used by hippocampal networks to store information. Aged spatial memory-impaired rats exhibit defective experience-dependent place field expansion plasticity. One possible explanation for this aged-associated deficit is alterations in glutamatergic function. In fact, both NMDAR- and AMPAR-mediated field excitatory postsynaptic potentials in CA1 decrease with aging. The current study investigated whether modulation of either AMPA or NDMA receptor activity could restore this experience-dependent plasticity by prolonging AMPAR activity with the ampakine CX516 and modulating the NMDAR with the noncompetitive antagonist memantine. The spatial firing characteristics of multiple CA1 pyramidal cells were monitored under both treatment conditions as aged rats repeatedly traversed a circular track. Compared to the saline baseline condition, acute administration of memantine, but not CX516, reinstated experience-dependent place field expansion. Taken together, these data suggest that pharmacological manipulation of the NMDAR can improve the function of hippocampal networks critical to optimal cognition in aging.
Evelyn F. McKnight Brain Institute, Life Sciences North Building, Room 384, University of Arizona, Tucson, AZ 85724, USA.
Sara N
SN
Burke
Andrew P
AP
Maurer
Zhiyong
Z
Yang
Zaneta
Z
Navratilova
Carol A
CA
Barnes
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D003213:Conditioning, Psychological / Q000502:physiology; D004149:Dioxoles / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D008297:Male; D008559:Memantine / Q000494:pharmacology; D008569:Memory Disorders / Q000503:physiopathology; D009068:Movement / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D017470:Receptors, Glutamate / Q000502:physiology*; D013028:Space Perception / Q000187:drug effects / Q000502:physiology*; D013826:Theta Rhythm
C097396:1-(quinoxalin-6-ylcarbonyl)piperidine; D004149:Dioxoles; D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D017470:Receptors, Glutamate; D008559:Memantine