Featured Finding Figure
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 the excitatory synaptic function in monkey DLPFC during postnatal development, 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 AMPA / NMDA ratio (see figure) and longer duration of NMDA-mediated synaptic currents, associated with greater sensitivity to the NR2B subunit-selective antagonist ifenprodil. In contrast, excitatory synaptic inputs in neurons from pre-adolescent (15 month-old) and adult (42 or 84 month-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.
Our results are relevant to current neurodevelopmental models of schizophrenia based in the observations that the efficacy of synaptic transmission is impaired in the illness. According to this model, the exuberant number of cortical synapses present prior to adolescence compensates for this synaptic dysfunction, and the pruning of these synapses during adolescence leads to the expression of the clinical consequences of the synaptic dysfunction. Our findings indicate that synaptic properties do not differ pre- and post-pruning, at least in the normal monkey DLPFC, suggesting that functionally mature pre-adolescent synapses might provide compensation via their excess number.
Gonzalez-Burgos G, Kröner S, Zaitsev A, Povysheva N, Krimer L, Barrionuevo G, Lewis DA: Functional maturation of excitatory synapses in layer 3 pyramidal neurons during postnatal development of the primate prefrontal cortex. Cereb Cortex 18: 626-637, 2008.

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David A. Lewis, M.D. | Department of Psychiatry | University of Pittsburgh
3811 O'Hara Street, Biomedical Science Tower W1654
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