Radiation-induced, lamina-specific deletion of neurons in the primate visual cortex

To examine the early determinants of cortical cytoarchitecture, we deleted specific neuronal classes in the primate visual cortex by ionizing irradiation at selected prenatal stages. Multiple doses of X-rays were delivered to the macaque monkey brain between embryonic day (E) 80 and E90 to block the division of cells destined to populate the superficial cortical layers, between E70 and E79 to eliminate neurons destined for the middle layers; and between E33 and E40 to delete neurons destined for the lateral geniculate nucleus (LGN) that project to the cortex. All animals were killed after birth, and their brains were processed for histological and electron microscopic analyses. Cell density and number in the LGN and visual cortex were determined by using three-dimensional, computer-aided morphometry. In animals irradiated with low doses (total of approximately 200 cGy) during the genesis of the LGN but before the onset of corticogenesis (E33-40), the LGN was reduced in both volume and number of neurons. Area 17 in these animals displayed only slight changes in cortical thickness, cell density, and area-specific cytoarchitectonic features, whereas the total surface devoted to area 17 was significantly diminished. In contrast, animals irradiated with low doses during the period of corticogenesis, after the completion of the LGN genesis, showed no significant change in the volume of the LGN or in the number of its cells. Moreover, in these animals, the surface of area 17 was not significantly altered, although the cortical layers generated at the time of irradiation had a significantly lower density and total number of cells, whereas the layers generated before and after the period of irradiation were spared. In contrast, cases exposed to high doses of X-ray (total > 300 cGy) showed more severe effects, including all layers. However, layers normally generated during irradiation were depleted and consisted of cell-sparse strata populated by densely packed neuropil (axons, small dendrites, dendritic spines, and synaptic boutons). These cell-sparse strata were situated deeper in the early irradiated animals than in the later irradiated animals, and their laminar position changed abruptly at the area 17/18 border. These results show that low doses of irradiation in a slowly developing primate brain can be used effectively to eliminate targeted classes of neurons before they reach their final position, providing an opportunity to examine the role of cell-cell interactions in the formation of circuitry and the role of specific cell classes in cortical development.