In the primate prefrontal cortex, the axon terminals of the chandelier class of inhibitory local circuit neurons have a distinctive time course of postnatal development. In this study, we sought to determine whether the axon terminals of other classes of local circuit neurons are also refined during postnatal development. We examined postnatal changes in the density of punctate structures immunoreactive for the calcium binding protein parvalbumin, which identifies a subset of gamma-aminobutyric acid (GABA) -containing terminals, in the prefrontal cortex of 35 rhesus monkeys ranging in age from newborn to adult. In area 46, the density of parvalbumin- immunoreactive puncta in the superficial and middle layers was extremely low in the newborn animals, then increased more than 10-fold to adult levels, which were achieved by 3 to 4 years of age. In layer V, a band of labeled puncta present in the newborn animals also increased in density until 3 to 4 years of age. Developmental changes of parvalbumin-immunoreactive puncta in area 9 were similar to those in area 46. In contrast, the density of punctate structures labeled with an antibody against a GABA membrane transporter (GAT-1) did not change across development, suggesting that the number of GABAergic terminals is stable over time, but that the level of parvalbumin protein within the terminals varies. The time course of the observed changes in these parvalbumin-labeled terminals is markedly different from that of parvalbumin-immunoreactive chandelier cell terminal clusters. These findings suggest that morphologically specialized classes of inhibitory interneurons assume prominence within the prefrontal cortical network at different stages of postnatal development.
The typical appearance of the clinical features of schizophrenia during late adolescence or early adulthood suggests that adolescence-related neurodevelopmental events may contribute to the pathophysiology of this disorder. Here the role that GABA-mediated inhibition in the dorsal lateral prefrontal cortex (DLPFC) plays in regulating working memory, a core cognitive process that matures late and that is disturbed in schizophrenia, is reviewed. Recent studies are summarized that demonstrate (1) that certain pre- and postsynaptic markers of GABA neurotransmission in the monkey DLPFC exhibit striking changes during adolescence, and (2) that these same markers are markedly altered in the DLPFC of subjects with schizophrenia. The implications of these findings for treatment and prevention strategies are discussed.
Accumulation of synaptic proteins, particularly those that are enriched in the postsynaptic density, is associated with resilience to psychosis in Alzheimer's disease. One candidate mechanism for this synaptic proteome compensation is alteration in levels of proteins that facilitate the transport of synaptic proteins to and from the postsynaptic density.
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