Submitted on November 21, 2007
Accepted on April 10, 2008
Altered dendritic integration in hippocampal granule cells of spatial learning-impaired, aged rats
Michael Krause1, Zhiyong Yang2, Geeta Rao, Frank P Houston2, and Carol A Barnes3*
1 Ernest Gallo Clinic and Research Center, 5858 Horton Street, Suite 200, Emeryville, California, 94608, United States; , United States
2 ARL Division of Neural Systems, Univeristy of Arizona, Tucson, Arizona, United States
3 University of Arizona, Tucson, Tucson, Arizona, United States; Department of Psychology, Univeristy of Arizona, Tucson, Arizona, United States; Department of Neurology, Univeristy of Arizona, Tucson, Arizona, United States; Evelyn F. McKnight Brain Institute, Univeristy of Arizona, Tucson, Arizona, United States
* To whom correspondence should be addressed. E-mail: carol{at}nsma.arizona.edu.
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 months) and aged (22-27 months) 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. With these recording methods, 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 aged slices, while it increased population spikes to a greater degree in 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.
