title: 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.
authors.affiliation: Department of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA 15213, USA.
authors.forename: Dianne A
authors.initials: DA
authors.lastname: Cruz
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Eggan
authors.forename: David A
authors.initials: DA
authors.lastname: Lewis
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D050485:GABA Plasma Membrane Transport Proteins; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D008253:Macaca mulatta; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D026901:Membrane Transport Proteins; D009415:Nerve Net / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism; D027361:Organic Anion Transporters; D017397:Prefrontal Cortex / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000737:chemistry / Q000378:metabolism; D017966:Pyramidal Cells / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid