Altered dendritic integration in hippocampal granule cells of spatial learning-impaired aged rats

Michael Krause, Zhiyong Yang, Geeta Rao, Frank P. Houston, C. A. Barnes

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)2769-2778
Number of pages10
JournalJournal of neurophysiology
Volume99
Issue number6
DOIs
StatePublished - Jun 1 2008

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ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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