Development of the calcium‐binding proteins parvalbumin and calbindin in monkey striate cortex

Abstract

The development of immunoreactivity for the calcium-binding proteins parvalbumin (PV) and calbindin-D28K (Cal) was studied in Macaca nemestrina striate cortex from fetal (F) 60 days to postnatal (P) 5 + years. We correlated changes in PV and Cal staining patterns with the well-documented developmental sequence for primate striate cortex neuron generation and maturation, synaptogenesis, and thalamocortical axon interactions in an attempt to deduce a functional role for these proteins. Our major findings is that Cal and PV have diametrically opposed developmental patterns except in layer 1. At F60 days both are present only in neurons of layer 1 and the number of labeled cell bodies and processes increases up to F125 days. Almost all Cal+ and PV+ cells in layer 1 disappear by P12 weeks. Cal is present by F113 days in pyramidal and stellate neurons, particularly layers 4-6. The numbers and staining density of cells in layers 2-6 increases up to birth and then both decline by P9-12 weeks. Supragranular layers show a second increase in Cal labeling from P20-36 weeks, and then there is a slow decline to the adult pattern which is reached by P1-2 years. Cell bodies in layers 4A, 4C alpha, and deep 4C beta are heavily Cal+ during pre- and early post-natal periods, but upper 4C beta remains unlabeled. PV is not seen until F155-162 days in layers 2-6. Large stellate and a few pyramidal cells appear first in layers 5/6 and 4C alpha, but PV+ stellate neurons are found in all layers except 4C beta by P6 weeks. Layer 4C beta contains a few PV+ cell bodies at P3 weeks, and light neuropile staining at P6 weeks, but then PV labeling rapidly increases so that by P12 weeks the density of 4C beta exceeds that of 4C alpha. Striate cortex has an adult pattern of cell number and neuropile density by P20 weeks. These developmental patterns suggest that the highest density of Cal cell body staining does not correlate with synaptogenesis, or the postnatal critical period of visually driven, binocular interactions. Rather Cal appears when lateral geniculate axons arrive in cortex, persists over the entire span of thalamocortical interactions, and disappears during the decline of cortical plasticity. The appearance of PV is highly correlated with the onset of complex visually driven activity at birth, while both the number of PV+ cell bodies and the density of PV+ neuropile reach adult levels coincident with the completion of thalamocortical connections.

Discrete reduction patterns of parvalbumin and calbindin D-28k immunoreactivity in the dorsal lateral geniculate nucleus and the striate cortex of adult macaque monkeys after monocular enucleation

“…The loss of CB-ir in a distinct population of neurons was pronounced in the superficial layers 2 and 4B of the denervated ODCs, where some of the weakly stained cells disappeared. Lightly labeled neurons have been shown to be pyramidal cells (Celio, 1990;Hendrickson et al, 1991;DeFelipe & Jones, 1992), and the presence of mRNA for CB was confirmed with in-situ hybridization (Sequier et al, 1990). We could not differentiate between the down regulation of the intracellular protein concentration by functional inactivation of these cells and their disappearance.…”

“…VanBrederode et al (1990) have demonstrated that very few GABAergic neurons contain both PV and CB, indicating that these mark specific subsets of interneurons. Whereas the occurrence of PV is restricted to GABAergic neurons, CB antibodies also lightly label some non-GABAergic pyramidal neurons (DeFelipe & Jones, 1992;Ferrer et al, 1992;Hendrickson et al, 1991;Sequier et al, 1990;VanBrederode et al, 1990).…”

Unravelling the development of the visual cortex: implications for plasticity and repair

“…Also, work by Conde and colleagues (Conde et al 1996;Cornelissen & Greenlee, 2000), using analysis of the laminar distribution of the calcium-binding proteins, calbindin-D28k and parvalbumin, demonstrated a hierarchical maturation of the ventral stream in the macaque, and has been used to correlate with specific events in cortical development, such as the formation of synapses and the onset of activity (Hendrickson et al 1991). For example, the expression of calbindin-D28k was associated with the establishment of synaptic connectivity, whereas the expression of parvalbumin was associated with the onset of visually driven activity (Hendrickson et al 1991).…”

Parvalbumin deficiency affects network properties resulting in increased susceptibility to epileptic seizures

“…control of pyramidal cell excitability (Blümcke et al, 1990;Cauli et al, 1997;DeFelipe et al, 1989DeFelipe et al, , 1993Hendrickson et al, 1991;Hendry et al, 1989;Lewis and Lund, 1990). Thus, it is expected that any alteration in the functional properties of the PVir interneurones will modify local inhibition, which eventually may affect the collective activity of the whole neuronal network.…”