Functional differentiation of cholecystokinin-containing interneurons destined for the cerebral cortex

Daniela Calvigioni, Zoltán Máté, János Fuzik, Fatima Girach, Ming Dong Zhang, A. Varró, Johannes Beiersdorf, Christian Schwindling, Yuchio Yanagawa, Graham J. Dockray, Chris J. McBain, Tomas Hökfelt, Gábor Szabó, Erik Keimpema, Tibor Harkany

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7 Citations (Scopus)


Although extensively studied postnatally, the functional differentiation of cholecystokinin (CCK)-containing interneurons en route towards the cerebral cortex during fetal development is incompletely understood. Here, we used CCKBAC/DsRed mice encoding a CCK promoter-driven red fluorescent protein to analyze the temporal dynamics of DsRed expression, neuronal identity, and positioning through high-resolution developmental neuroanatomy. Additionally, we developed a dual reporter mouse line (CCKBAC/DsRed::GAD67gfp/+) to differentiate CCK-containing interneurons from DsRed+ principal cells during prenatal development. We show that DsRed is upregulated in interneurons once they exit their proliferative niche in the ganglionic eminence and remains stably expressed throughout their long-distance migration towards the cerebrum, particularly in the hippocampus. DsRed+ interneurons, including a cohort coexpressing calretinin, accumulated at the palliosubpallial boundary by embryonic day 12.5. Pioneer DsRed+ interneurons already reached deep hippocampal layers by embryonic day 14.5 and were morphologically differentiated by birth. Furthermore, we probed migrating interneurons entering and traversing the cortical plate, as well as stationary cells in the hippocampus by patch-clamp electrophysiology to show the first signs of Na+ and K+ channel activity by embryonic day 12.5 and reliable adult-like excitability by embryonic day 18.5. Cumulatively, this study defines key positional, molecular, and biophysical properties of CCK+ interneurons in the prenatal brain.

Original languageEnglish
Pages (from-to)2453-2468
Number of pages16
JournalCerebral Cortex
Issue number4
Publication statusPublished - Jan 1 2017



  • Cortical plate
  • Light sheet microscopy
  • Migration
  • Specification
  • Synaptogenesis
  • Transgene reporter

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Calvigioni, D., Máté, Z., Fuzik, J., Girach, F., Zhang, M. D., Varró, A., Beiersdorf, J., Schwindling, C., Yanagawa, Y., Dockray, G. J., McBain, C. J., Hökfelt, T., Szabó, G., Keimpema, E., & Harkany, T. (2017). Functional differentiation of cholecystokinin-containing interneurons destined for the cerebral cortex. Cerebral Cortex, 27(4), 2453-2468.