Thalamo-cortical axons regulate the radial dispersion of neocortical GABAergic interneurons

Sabrina Zechel, Yasushi Nakagawa, Carlos F. Ibáñez

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Neocortical GABAergic interneuron migration and thalamo-cortical axon (TCA) pathfinding follow similar trajectories and timing, suggesting they may be interdependent. The mechanisms that regulate the radial dispersion of neocortical interneurons are incompletely understood. Here we report that disruption of TCA innervation, or TCA-derived glutamate, affected the laminar distribution of GABAergic interneurons in mouse neocortex, resulting in abnormal accumulation in deep layers of interneurons that failed to switch from tangential to radial orientation. Expression of the KCC2 cotransporter was elevated in interneurons of denervated cortex, and KCC2 deletion restored normal interneuron lamination in the absence of TCAs. Disruption of interneuron NMDA receptors or pharmacological inhibition of calpain also led to increased KCC2 expression and defective radial dispersion of interneurons. Thus, although TCAs are not required to guide the tangential migration of GABAergic interneurons, they provide crucial signals that restrict interneuron KCC2 levels, allowing coordinated neocortical invasion of TCAs and interneurons.

Original languageEnglish (US)
Article numbere20770
JournaleLife
Volume5
Issue numberDECEMBER2016
DOIs
StatePublished - Dec 9 2016

Bibliographical note

Funding Information:
Knut och Alice Wallenbergs Stiftelse Carlos F Ibáñez Karolinska Institutet Carlos F Ibáñez National University of Singapore Carlos Ibáñez Wenner-Gren Foundation Sabrina Zechel Vetenskapsrådet Carlos Ibáñez The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Publisher Copyright:
© Zechel et al.

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