Cerebral Cortex Advance Access originally published online on June 24, 2007
Cerebral Cortex 2008 18(3):626-637; doi:10.1093/cercor/bhm095
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Functional Maturation of Excitatory Synapses in Layer 3 Pyramidal Neurons during Postnatal Development of the Primate Prefrontal Cortex
1 Department of Psychiatry, 2 Department of Neuroscience, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA, 3 Current address: Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA
Address correspondence to Dr Guillermo Gonzalez-Burgos, Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, W1651 Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA 15261, USA. Email: gburgos{at}pitt.edu.
In the primate dorsolateral prefrontal cortex (DLPFC), the density of excitatory synapses decreases by 40–50% during adolescence. Although such substantial circuit refinement might underlie the adolescence-related maturation of working memory performance, its functional significance remains poorly understood. The consequences of synaptic pruning may depend on the properties of the eliminated synapses. Are the synapses eliminated during adolescence functionally immature, as is the case during early brain development? Or do maturation-independent features tag synapses for pruning? We examined excitatory synaptic function in monkey DLPFC during postnatal development by studying properties that reflect synapse maturation in rat cortex. In 3-month-old (early postnatal) monkeys, excitatory inputs to layer 3 pyramidal neurons had immature properties, including higher release probability, lower 
-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/N-methyl-D-aspartate (NMDA) ratio, and longer duration of NMDA-mediated synaptic currents, associated with greater sensitivity to the NMDA receptor subunit B (NR2B) subunit–selective antagonist ifenprodil. In contrast, excitatory synaptic inputs in neurons from preadolescent (15 months old) and adult (42 or 84 months old) monkeys had similar functional properties. We therefore conclude that the contribution of functionally immature synapses decreases significantly before adolescence begins. Thus, remodeling of excitatory connectivity in the DLPFC during adolescence may occur in the absence of widespread maturational changes in synaptic strength.
Key Words: adolescence • EPSC • glutamate • maturation • NMDA • NR2B
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