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

Nature Neuroscience volume 16, pages 10321041 (2013) | Download Citation

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.

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Acknowledgements

D. Abebe and X. Yuan provided expert technical assistance. We thank S. Anderson (University of Pennsylvania) for providing the Nkx2-1-cre driver line and G. Fishell (New York University) for providing the RCE reporter line. This work was supported by a Eunice Kennedy-Shriver National Institute of Child Health and Human Development intramural award to C.J.M. and a PRAT Fellowship to J.A.M.

Author information

Author notes

    • Jose A Matta

    Present address: Janssen Research & Discovery, La Jolla, California, USA.

Affiliations

  1. Program in Developmental Neurobiology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.

    • Jose A Matta
    • , Kenneth A Pelkey
    • , Michael T Craig
    • , Ramesh Chittajallu
    • , Brian W Jeffries
    •  & Chris J McBain

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Contributions

J.A.M., K.A.P. and C.J.M. conceived of the project, designed experiments and wrote the manuscript. J.A.M., K.A.P., M.T.C. and R.C. conducted experiments and analyzed the data. B.W.J. provided technical assistance with cell recoveries and drawings. C.J.M. and K.A.P. supervised the project.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Kenneth A Pelkey.

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DOI

https://doi.org/10.1038/nn.3459

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