title: Normal aging results in decreased synaptic excitation and increased synaptic inhibition of layer 2/3 pyramidal cells in the monkey prefrontal cortex.
abstract: 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 (< or =12 years old) and aged (> or =19 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 GABAA 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.
authors.affiliation: Center for Behavioral Development, Department of Psychiatry, Boston University School of Medicine, Boston, MA 02118, USA. jluebke@bu.edu
authors.forename: J I
authors.initials: JI
authors.lastname: Luebke
authors.forename: Y-M
authors.initials: YM
authors.lastname: Chang
authors.forename: T L
authors.initials: TL
authors.lastname: Moore
authors.forename: D L
authors.initials: DL
authors.lastname: Rosene
mesh_terms: D000375:Aging; D000818:Animals; D003071:Cognition / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D008253:Macaca mulatta; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology*; D011963:Receptors, GABA-A / Q000378:metabolism; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D011963:Receptors, GABA-A