Changes in GABAA receptor-mediated synaptic transmission during postnatal development of monkey dorsolateral prefrontal cortex

MIYAMAE T; PAFUNDO DE; YOSHINO H; ROTARU D; ERMENTROUT GB; GONZALEZ-BURGOS G; LEWIS DA

New Orleans, LA

Congreso; 42nd annual meeting of the Society for Neuroscience; 2012

Society for Neuroscience

In the rodent brain, functional maturation of cortical GABA synapses takes place mostly during postnatal days 1-28, prior to the onset of adolescence. In the primate brain, which undergoes a protracted maturation extending throughout adolescence and into early adulthood, cortical GABA synapse maturation is largely unexplored. To determine whether GABA synapses in the primate dorsolateral prefrontal cortex (PFC) display functional changes during postnatal brain development, we recorded GABAAR-mediated inhibitory postsynaptic currents (IPSCs) from layer 3 pyramidal cells (PCs) in the PFC of neonatal, preadolescent, adolescent and young adult rhesus monkeys (ages, in months: 1, 9-12, 34 and 60-64, respectively). We found that spontaneous IPSC (sIPSC) amplitude increased between the neonatal and adolescence periods and remained large in adulthood. Furthermore, the sIPSC rise and decay time became significantly faster between neonatal and preadolescent age. Neonatal PCs showed a cluster of sIPSCs with slow rise time and small amplitude that was absent in PCs from older ages. One possibility is that neonatal PCs are electrotonically more compact, therefore allowing detection at the cell soma of a larger fraction of sIPSCs of distal origin. However, preliminary analysis suggested that neonatal PCs had nearly mature intrinsic physiological properties and dendritic tree morphology and, moreover, had fewer sIPSCs with fast rise time, arguing against the idea of a different dendrite-to-soma electrical coupling. To test the hypothesis that sIPSCs with slow kinetics in neonatal PCs originate in immature perisomatic synapses, we studied IPSCs evoked by focal extracellular stimulation applied near the PC soma. In adult PCs, IPSCs evoked by perisomatic stimulation (psIPSCs) had fast rise times, consistent with predominant activation of perisomatic GABA synapses, and also relatively fast decay time. The rise and decay times of psIPSCs were similarly fast in adolescent and preadolescent PCs, but were significantly slower in neonatal PCs. Similar age-related changes were observed in agatoxin-resistant/endocannabinoid-sensitive and in agatoxin-sensitive psIPSCs, presumed to originate in cholecystokinin- and parvalbumin-positive basket cells, respectively. Simulations in a computational model suggested that the age-related changes in GABA synapses produce a PFC network with enhanced capacity to generate gamma band oscillations via recurrent excitation-inhibition. Therefore, the developmental changes in function of GABA synapses onto PCs may contribute to the maturation of cognitive functions dependent on gamma band activity in the PFC network.