In Patas monkey, glutamic acid decarboxylase-67 and reelin mRNA coexpression varies in a manner dependent on layers and cortical areas

Abstract

In nonhuman and human primates, reelin immunoreactivity is expressed consistently in gamma-aminobutyric acid (GABA)-ergic interneurons of the three upper cortical layers (Impagnatiello et al. [1998] Proc. Natl. Acad. Sci. U S A 95:15718-15723; Rodriguez et al. [2000] Proc. Natl. Acad. Sci. U S A 97:3550-3555). To understand in detail the pattern of reelin synthesis in GABAergic interneurons of primate neocortex, a quantitative analysis of reelin and of glutamic acid decarboxylase-67 (GAD(67)) mRNA-positive neurons as well as a quantitative analysis of total neuronal density measured by neuron-specific nuclear protein (NeuN) immunoreactivity was carried out in Patas monkey neocortex (Brodmann's areas 2, 3, 4, 6, 9, 17, 18, and 24). Reelin mRNA is expressed in every cortical area and layer studied, but layer II of each cortical area consistently revealed the largest neuronal population expressing reelin mRNA compared with other layers. The percentages of GAD(67)-positive neurons in each layer of the eight cortical areas were 83-98% in layer I, 55-64% in layer II, 37-49% in layer III, 71-89% in layer IV, 54-68% in layer V, and 71-85% in layer VI. The percentages of GABAergic neurons expressing reelin were 86-100% in layer I, 76-84% in layer II, 52-96% in layer III, 23-33% in layer IV, 33-57% in layer V, and 34-54% in layer VI. These findings suggest that there may be two classes of GABAergic neurons that can be differentiated by their ability to express reelin mRNA and reelin protein. This differentiation may have a functional significance, considering that reelin is secreted into the extracellular matrix, where it plays a putative role in the maturation of newly formed dendritic spines and binds selectively to dendritic shafts and to spine postsynaptic densities and presumably to integrin receptors, including alpha(3) subunits (Rodriguez et al. [2000]).