Altered Dendritic Integration in Hippocampal Granule Cells of Spatial Learning-Impaired Aged Rats

• Published in: Journal of neurophysiology Vol. 99; no. 6; pp. 2769 - 2778
• Main Authors: Krause, Michael, Yang, Zhiyong, Rao, Geeta, Houston, Frank P, Barnes, C. A
• Format: Journal Article
• Language: English
• Published: United States Am Phys Soc 01.06.2008; American Physiological Society
• Subjects: 6-Cyano-7-nitroquinoxaline-2,3-dione - pharmacology; Aging; Analysis of Variance; Animals; Behavior, Animal; Dendrites - pathology; Dose-Response Relationship, Radiation; Electric Stimulation - methods; Excitatory Amino Acid Antagonists - pharmacology; Hippocampus - pathology; In Vitro Techniques; Learning Disorders - pathology; Male; Maze Learning - physiology; Membrane Potentials - drug effects; Membrane Potentials - physiology; Membrane Potentials - radiation effects; Neurons - pathology; Patch-Clamp Techniques; Rats; Rats, Inbred F344; Reaction Time - drug effects; Reaction Time - physiology; Reaction Time - radiation effects; Space Perception - physiology; Valine - analogs & derivatives; Valine - pharmacology
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.01278.2007

1 Arizona Research Laboratories Division of Neural Systems, Memory and Aging, Departments of 2 Psychology and 3 Neurology, 4 Evelyn F. McKnight Brain Institute, University of Arizona, Tucson, Arizona Submitted 21 November 2007; accepted in final form 10 April 2008 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 I h or inwardly rectifying potassium currents, during aging. Address for reprint requests and other correspondence: C. A. Barnes, University of Arizona, Evelyn F. McKnight Brain Institute, Life Sciences North Bldg., Rm. 384, Tucson, AZ 85724 (E-mail: carol{at}nsma.arizona.edu )