41,42 The potential contribution of excitatory synapse pruning during adolescence to disease-related changes in DLPFC function depends, in part, on the functional properties of the synapses that are pruned. During early brain development, pruned synapses are functionally immature. Immature glutamate synapses are relatively weak and their maturation involves an activity-dependent increase in strength. Such activity-dependent strengthening might underlie synapse stabilization,

and thus mark for elimination the immature synapses that are not strengthened.43,44 However, recent findings in the developing monkey DLPFC indicate that the excitatory-inputs to layer 3 pyramidal Inhibitors,research,lifescience,medical neurons mature functionally Inhibitors,research,lifescience,medical during the age range when they are present in high density and before synaptic pruning begins.45 Thus, these data suggest that the substantial remodeling

of excitatory connectivity of the primate DLPFC during adolescence primarily involves the elimination of mature synapses, and that some other factor, such as the neuronal source of input, somehow tags mature synapses for pruning.46 Thus, the Inhibitors,research,lifescience,medical presence of functionally mature synapses prior to adolescence supports the hypothesis that the excess in excitatory synapse number prior to adolescence might be able to compensate for a molecular based dysfunction of these synapses in individuals with schizophrenia, and thereby forestall the appearance of the clinical features of the illness until synapse number falls below some

critical threshold.40 Neuroplasticity of inhibitory cortical connections in schizophrenia Prefrontal inhibitory neurotransmission is altered in schizophrenia Studies from multiple Inhibitors,research,lifescience,medical laboratories have consistently found lower levels of the mRNA for the 67 kilodalton isoform of glutamic acid decarboxylase (GAD67), the principal synthesizing enzyme for y-aminobutyric acid (GABA), in Inhibitors,research,lifescience,medical the DLPFC of subjects with schizophrenia.16,22-47,52 At the cellular level, the expression of GAD67 mRNA was not detectable in -25% to 35% of GABA neurons in layers 15 of the DLPFC, but the remaining GABA neurons exhibited normal levels of GAD67 mRNA.16-47 Similarly, expression of the mRNA for the GABA membrane transporter (GAT1), a protein inhibitor Paclitaxel responsible for reuptake of released GABA into nerve terminals, was decreased in a similar minority of GABA neurons.53 These findings suggest that both the synthesis and Anacetrapib reuptake of GABA are lower in a subset of DLPFC neurons in schizophrenia. Subclasses of cortical GABA neurons can be distinguished on the basis of a number of molecular, electro-physiological, and anatomical properties. For example, the affected GABA neurons in schizophrenia include the subclass that selleck chemical EPZ-5676 contain the calcium-binding protein, parvalbumin (PV), which comprise -25% of GABA neurons in the primate DLPFC.