Postnatal development of pre‐ and postsynaptic GABA markers at chandelier cell connections with pyramidal neurons in monkey prefrontal cortex

Abstract

The protracted postnatal maturation of the primate prefrontal cortex (PFC) is associated with substantial changes in the number of excitatory synapses on pyramidal neurons, whereas the total number of inhibitory synapses appears to remain constant. In this study, we sought to determine whether the developmental changes in excitatory input to pyramidal cells are paralleled by changes in functional markers of inhibitory inputs to pyramidal neurons. The chandelier subclass of gamma-aminobutyric acid (GABA) neurons provides potent inhibitory control over pyramidal neurons by virtue of their axon terminals, which form distinct vertical structures (termed cartridges) that synapse at the axon initial segment (AIS) of pyramidal neurons. Thus, we examined the relative densities, laminar distributions, and lengths of presynaptic chandelier axon cartridges immunoreactive for the GABA membrane transporter 1 (GAT1) or the calcium-binding protein parvalbumin (PV) and of postsynaptic pyramidal neuron AIS immunoreactive for the GABA(A) receptor alpha(2) subunit (GABA(A) alpha(2)) in PFC area 46 of 38 rhesus monkeys (Macaca mulatta). From birth through 2 years of age, the relative densities and laminar distributions of these three markers exhibited different trajectories, suggesting developmental shifts in the weighting of at least some factors that determine inhibition at the AIS. In contrast, from 2 to 4 years of age, all three markers exhibited similar declines in density and length that paralleled the periadolescent pruning of excitatory synapses to pyramidal neurons. Across development, the predominant laminar location of PV-labeled cartridges and GABA(A) alpha(2)-immunoreactive AIS shifted from the middle to superficial layers, whereas the laminar distribution of GAT1-positive cartridges did not change. Together, these findings suggest that the maturation of inhibitory inputs to the AIS of PFC pyramidal neurons is a complex process that may differentially affect the firing patterns of subpopulations of pyramidal neurons at specific postnatal time points.

GABAergic Neurons Immunoreactive for Calcium Binding Proteins are Reduced in the Prefrontal Cortex in Major Depression

“…These cells differ by morphology, type of contacts with pyramidal neurons, pattern of firing, and monoaminergic innervation. PV-IR interneurons correspond to basket or chandelier cells, make contacts on somata and axonal initial segments of pyramidal neurons and regulate cortical output activity (Baimbridge et al, 1992;Cauli et al, 1997;Conde et al, 1994;Cruz et al, 2003;DeFelipe, 1989DeFelipe, , 1997Gabbott et al, 1997;Lewis and Lund, 1990;Lund and Lewis, 1993;Somogyi et al, 1998). PV-IR neurons have physiological properties characteristic of fast-spiking interneurons Kubota, 1993, 1997;Zaitsev et al, 2005).…”

Does schizophrenia arise from oxidative dysregulation of parvalbumin-interneurons in the developing cortex?

“…Oscillatory activity in the gamma range also begins during this second postnatal week, and matures throughout the following weeks to reach adult levels by the end of the adolescent period (Doischer et al, 2008). In non-human primates, the appearance of parvalbumin expression and development of PV-synaptic contacts begins at around 3 months of age, and develops profusely throughout childhood and adolescence (Reynolds and Beasley 2001;Cruz et al, 2003). During adolescence, however, the restructuring and pruning of synaptic contacts reduces the levels to those found in adulthood (Cruz et al, 2003).…”

“…In non-human primates, the appearance of parvalbumin expression and development of PV-synaptic contacts begins at around 3 months of age, and develops profusely throughout childhood and adolescence (Reynolds and Beasley 2001;Cruz et al, 2003). During adolescence, however, the restructuring and pruning of synaptic contacts reduces the levels to those found in adulthood (Cruz et al, 2003). Cortical neural synchrony and cognitive performance also show a protracted maturation in humans, reaching mature levels only in early adulthood after a period of decreased cognitive performance and synchrony during adolescence (Uhlhaas et al, 2009).…”

“…These results suggest that PV-interneurons are more resistant to the effects of NMDA-R antagonists during the rodent equivalent to the adolescence period in humans. The overwhelming proliferation of PV-synaptic contacts observed before adolescence (Cruz et al, 2003), as well as the slow functional maturation of PV-inhibitory network (Doischer et al, 2008;Okaty et al, 2009) may explain the lack of pro-psychotic effects of NMDA-R antagonists before early adulthood. However, hormonal influences or changes in receptor-expression patterns (Okaty et al,.…”

EEG gamma-band synchronization in visual coding from childhood to old age: Evidence from evoked power and inter-trial phase locking

“…Most investigations addressing the effects of early developmental changes in neuromodulation on neuronal synchronization were carried out in animal models and primarily refer to intrauterine and early postnatal phases of development (Ben-Ari et al, 2004;Le Van Quyen et al, 2006). Recent studies using rat and primate models also report protracted development of neurotransmitter systems well into adolescence (Cruz et al, 2003;Hashimoto et al, in press). For instance, work with rodents indicates that the dopaminergic modulation of interneurons matures particularly late in the course of development (Tseng and O'Donnell, 2007).…”