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Publication : Functional Differentiation of Cholecystokinin-Containing Interneurons Destined for the Cerebral Cortex.

First Author  Calvigioni D Year  2017
Journal  Cereb Cortex Volume  27
Issue  4 Pages  2453-2468
PubMed ID  27102657 Mgi Jnum  J:241330
Mgi Id  MGI:5901807 Doi  10.1093/cercor/bhw094
Citation  Calvigioni D, et al. (2017) Functional Differentiation of Cholecystokinin-Containing Interneurons Destined for the Cerebral Cortex. Cereb Cortex 27(4):2453-2468
abstractText  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.
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