Aging alters dendritic morphology, input resistance, and inhibitory signaling in dentate granule cells of the rhesus monkey.

The neural substrates of age-related hippocampal dysfunction in primates are poorly understood. This issue was addressed with combined intracellular biocytin filling and whole-cell patch clamp recordings of intrinsic membrane properties and inhibitory postsynaptic currents (IPSCs) in dentate granule cells in in vitro slices prepared from behaviorally characterized young (<11 years old) and aged (>24 years old) rhesus monkeys. Six of nine aged monkeys were significantly impaired in performance on the hippocampally mediated delayed nonmatch to sample (DNMS) task at a 2-minute delay. Morphometric analyses showed that cells from aged monkeys had significantly reduced vertical dendritic extents and distal dendritic branching but increased proximal dendritic branching. Intrinsic membrane and action potential properties did not differ between cells from young and aged monkeys with the exception of a small but significant increase in input resistance with age. The frequency, amplitude, and rise time of gamma-aminobutyric acid (GABA)(A) receptor-mediated miniature IPSCs were not significantly different in cells from young vs. aged monkeys. However, the miniature IPSC decay time constant and the benzodiazepine potentiation of this decay time constant were both significantly increased in cells from aged monkeys. These differences in the properties of dentate granule cells correlated positively with age but not specifically with impairment on the DNMS 2-minute delay task. Nevertheless, these changes in dendritic morphology, input resistance, and inhibitory signaling properties may be part of a constellation of subtle functional changes contributing to age-associated cognitive impairment. Copyright 2003 Wiley-Liss, Inc.