Developmental changes in calretinin expression in GABAergic and nonGABAergic neurons in monkey striate cortex.

The development of the calcium-binding protein calretinin (CaR) and its co-localization with GABA was studied in the striate cortex of Macaca monkeys from fetal day (Fd) 45 to adult. At Fd45, early neurons resembling Cajal-Retzius cells are stained in the marginal zone (MZ). At Fd55 the MZ is filled with CaR+ Cajal-Retzius cells and their processes, and scattered CaR+ cells are also found in deep cortical plate (CP), intermediate zone (IZ), and subventricular zone (SVZ). At Fd66, a band of CaR+ fibers appears in the IZ, corresponding to the location of the geniculocortical axons. This fiber band labels heavily until Fd130 but then ceases to be immunoreactive by postnatal (P) 16 weeks. At Fd85-101, the number of CaR+ cells in the CP, SVZ, and ventricular zone (VZ) reaches its highest cell density. After Fd130, CaR+ cells are concentrated in layer II and upper layer III, and this distribution changes little into adulthood. After mid-gestation, there is a progressive loss of CaR+ cell bodies and processes in the MZ, and these are rare in the adult cortex. Just before birth, a weakly stained CaR+ cell band appears in layer IVA at the border between layer IVA and IVB, but this band disappears immediately after birth. Another CaR+ cell band appears transiently in upper layer V just below the border with layers IV at P6 months. These results suggest that CaR is expressed early in fetal development in the cell populations that are immunoreactive for CaR in the adult. However, developmental events related to cortical maturation during late prenatal and early postnatal stages result in transient expression of CaR in neurons that are not immunoreactive for CaR in the adult. CaR-immunoreactivity is colocalized with GABA in almost all CaR+ cells with the exception of Cajal-Retzius cells in the MZ and some large cells observed at Fd70-101 in the VZ. The band of CaR+ fibers in the IZ is GABA-. At Fd90, almost all (> 96%) CaR+ cells are GABA+ in the CP and the first developed layers V/VI. This percentage declines later, so that on average 80% of CaR+ cells are GABA+ in adult cortex. At Fd135, 53% of GABA+ neurons located in layers II/III are CaR+; this percentage declines to 37% in the adult. These double-label patterns suggest that early in fetal development the majority of GABA+ cells stain for CaR and that expression of CaR may be related to the migration of these neurons into the cortical plate. Once they attain their final position in the cortex many GABA+ cells loose CaR-immunoreactivity, so that in postnatal life only a minority of GABA+ neurons contain this calcium-binding protein.