title: Functional Maturation of GABA Synapses During Postnatal Development of the Monkey Dorsolateral Prefrontal Cortex.
abstract: Development of inhibition onto pyramidal cells may be crucial for the emergence of cortical network activity, including gamma oscillations. In primate dorsolateral prefrontal cortex (DLPFC), inhibitory synaptogenesis starts in utero and inhibitory synapse density reaches adult levels before birth. However, in DLPFC, the expression levels of γ-aminobutyric acid (GABA) synapse-related gene products changes markedly during development until young adult age, suggesting a highly protracted maturation of GABA synapse function. Therefore, we examined the development of GABA synapses by recording GABAAR-mediated inhibitory postsynaptic currents (GABAAR-IPSCs) from pyramidal cells in the DLPFC of neonatal, prepubertal, peripubertal, and adult macaque monkeys. We found that the decay of GABAAR-IPSCs, possibly including those from parvalbumin-positive GABA neurons, shortened by prepubertal age, while their amplitude increased until the peripubertal period. Interestingly, both GABAAR-mediated quantal response size, estimated by miniature GABAAR-IPSCs, and the density of GABAAR synaptic appositions, measured with immunofluorescence microscopy, were stable with age. Simulations in a computational model network with constant GABA synapse density showed that the developmental changes in GABAAR-IPSC properties had a significant impact on oscillatory activity and predicted that, whereas DLPFC circuits can generate gamma frequency oscillations by prepubertal age, mature levels of gamma band power are attained at late stages of development.
authors.affiliation: Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Gonzalez-Burgos
authors.affiliation: Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Takeaki
authors.initials: T
authors.lastname: Miyamae
authors.affiliation: Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA Current address: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, USA.
authors.forename: Diego E
authors.initials: DE
authors.lastname: Pafundo
authors.affiliation: Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA Current address: Department of Psychiatry, Nara Medical University, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yoshino
authors.affiliation: Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA Current address: Department of Integrative Neurophysiology, Vrije Universiteit, Amsterdam, Netherlands.
authors.forename: Diana C
authors.initials: DC
authors.lastname: Rotaru
authors.affiliation: Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Gil
authors.initials: G
authors.lastname: Hoftman
authors.affiliation: Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Dibyadeep
authors.initials: D
authors.lastname: Datta
authors.affiliation: Department of Statistics, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Mathematics, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Mahjub
authors.initials: M
authors.lastname: Hammond
authors.affiliation: Department of Statistics, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Allan R
authors.initials: AR
authors.lastname: Sampson
authors.affiliation: Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Fish
authors.affiliation: Department of Mathematics, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: G Bard
authors.initials: GB
authors.lastname: Ermentrout
authors.affiliation: Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Lewis
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008253:Macaca mulatta; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects; D017397:Prefrontal Cortex / Q000166:cytology* / Q000254:growth & development*; D011724:Pyridazines / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D020867:omega-Agatoxin IVA / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D011724:Pyridazines; D020867:omega-Agatoxin IVA; D005680:gamma-Aminobutyric Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C049853:gabazine; C013411:biocytin; D008239:Lysine
keywords: GABA; cognitive function; dorsolateral prefrontal cortex; gamma oscillations; inhibition; inhibitory postsynaptic current; nonhuman primate