Developmental origin dictates interneuron AMPA and NMDA receptor subunit composition and plasticity

Matta, J. A., Pelkey, K. A., Craig, M. T. , Chittajallu, R., Jeffries, B. W. and McBain, C. J. (2013) Developmental origin dictates interneuron AMPA and NMDA receptor subunit composition and plasticity. Nature Neuroscience, 16(8), pp. 1032-1041. (doi: 10.1038/nn.3459) (PMID:23852113) (PMCID:PMC4132661)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Craig, Dr Mick
Authors: Matta, J. A., Pelkey, K. A., Craig, M. T., Chittajallu, R., Jeffries, B. W., and McBain, C. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Nature Neuroscience
Publisher:Nature Publishing Group
ISSN:1097-6256
ISSN (Online):1546-1726
Published Online:14 July 2013

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