Altered dendritic integration in hippocampal granule cells of spatial learning-impaired aged rats.
Glutamatergic transmission at central synapses undergoes activity-dependent and developmental changes. In the hippocampal dentate gyrus, the non-N-methyl d-aspartate (NMDA) receptor component of field excitatory postsynaptic potentials (fEPSPs) increases with age in Fischer-344 rats. This effect may not depend on the animal's activity or experience but could be part of the developmental process. Age-dependent differences in synaptic transmission at the perforant path-granule cell synapse may be caused by changes in non-NMDA and NMDA receptor-mediated currents. To test this hypothesis, we compared whole cell excitatory postsynaptic currents (EPSCs) in dentate granule cells evoked by perforant path stimulation in young (3-4 mo) and aged (22-27 mo) Fischer-344 rats using a Cs+-based intracellular solution. Aged animals as a group showed spatial learning and memory deficits in the Morris water maze. Using whole cell recordings, slope conductances of both non-NMDA and NMDA EPSCs at holding potentials -10 to +50 mV were significantly reduced in aged animals and the non-NMDA/NMDA ratio in aged animals was found to be significantly smaller than in young animals. In contrast, we detected no differences in basic electrophysiological parameters, or absolute amplitudes of non-NMDA and NMDA EPSCs. Extracellular Cs+ increased the fEPSP in young slices to a greater degree than was found in the aged slices, while it increased population spikes to a greater degree in the aged rats. Our results not only provide evidence for reduced glutamatergic synaptic responses in Fischer-344 rats but also point to differential changes in Cs+-sensitive dendritic conductances, such as Ih or inwardly rectifying potassium currents, during aging.
Krause
Michael
M
Arizona Research Laboratories, Division of Neural Systems, Memory and Aging, University of Arizona, Tucson, AZ 85724, USA.
Yang
Zhiyong
Z
Rao
Geeta
G
Houston
Frank P
FP
Barnes
C A
CA
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D003712:Dendrites / Q000473:pathology*; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000473:pathology*; D066298:In Vitro Techniques; D007859:Learning Disabilities / Q000473:pathology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000473:pathology*; D018408:Patch-Clamp Techniques; D051381:Rats; D011916:Rats, Inbred F344; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D013028:Space Perception / Q000502:physiology*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine