title: Developmental origin dictates interneuron AMPA and NMDA receptor subunit composition and plasticity.
abstract: Disrupted excitatory synapse maturation in GABAergic interneurons may promote neuropsychiatric disorders such as schizophrenia. However, establishing developmental programs for nascent synapses in GABAergic cells is confounded by their sparsity, heterogeneity and late acquisition of subtype-defining characteristics. We investigated synaptic development in mouse interneurons targeting cells by lineage from medial ganglionic eminence (MGE) or caudal ganglionic eminence (CGE) progenitors. MGE-derived interneuron synapses were dominated by GluA2-lacking AMPA-type glutamate receptors (AMPARs), with little contribution from NMDA-type receptors (NMDARs) throughout development. In contrast, CGE-derived cell synapses had large NMDAR components and used GluA2-containing AMPARs. In neonates, both MGE- and CGE-derived interneurons expressed primarily GluN2B subunit-containing NMDARs, which most CGE-derived interneurons retained into adulthood. However, MGE-derived interneuron NMDARs underwent a GluN2B-to-GluN2A switch that could be triggered acutely with repetitive synaptic activity. Our findings establish ganglionic eminence-dependent rules for early synaptic integration programs of distinct interneuron cohorts, including parvalbumin- and cholecystokinin-expressing basket cells.
authors.affiliation: Program in Developmental Neurobiology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Matta
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Pelkey
authors.forename: Michael T
authors.initials: MT
authors.lastname: Craig
authors.forename: Ramesh
authors.initials: R
authors.lastname: Chittajallu
authors.forename: Brian W
authors.initials: BW
authors.lastname: Jeffries
authors.forename: Chris J
authors.initials: CJ
authors.lastname: McBain
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers; D019070:Cell Lineage; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D059330:GABAergic Neurons / Q000166:cytology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D007395:Interneurons / Q000145:classification / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019579:Neocortex / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D009419:Nerve Tissue Proteins / Q000032:analysis; D009473:Neuronal Plasticity; D009928:Organ Specificity; D018091:Receptors, AMPA / Q000032:analysis / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D009435:Synaptic Transmission; D013687:Telencephalon / Q000166:cytology / Q000196:embryology*
chemical_list: D015415:Biomarkers; C121001:NR2B NMDA receptor; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C104722:glutamate receptor ionotropic, AMPA 2