Normal aging results in decreased synaptic excitation and increased synaptic inhibition of layer 2/3 pyramidal cells in the monkey prefrontal cortex

Executive system function, mediated largely by the prefrontal cortex (PFC), often declines significantly with normal aging in humans and non-human primates. The neural substrates of this decline are unknown, but age-related changes in the structural properties of PFC neurons could lead to altered synaptic signaling and ultimately to PFC dysfunction. The present study addressed this issue using whole-cell patch clamp assessment of excitatory and inhibitory postsynaptic currents (PSCs) in layer 2/3 pyramidal cells in in vitro slices of the PFC from behaviorally characterized young (less than or equal to12 years old) and aged (greater than or equal to19 years old) rhesus monkeys. Behaviorally, aged monkeys were significantly impaired in performance on memory and executive system function tasks. Physiologically, the frequency of spontaneous glutamate receptor-mediated excitatory PSCs was significantly reduced in cells from aged monkeys, while the frequency of spontaneous GABA(A) receptor-mediated inhibitory PSCs was significantly increased. In contrast, there was no effect of age on the frequency, amplitude, rise time or decay time of action potential-independent miniature excitatory and inhibitory PSCs. The observed change in excitatory-inhibitory synaptic balance likely leads to significantly altered signaling properties of layer 2/3 pyramidal cells in the PFC with age. (C) 2004 Published by Elsevier Ltd on behalf of IBRO.