Neocortical integration of transplanted GABA progenitor cells from wild type and GABA(B) receptor knockout mouse donors

Neurosci Lett. 2014 Feb 21:561:52-7. doi: 10.1016/j.neulet.2013.11.012. Epub 2013 Nov 26.

Abstract

Most cortical interneurons originate in a region of the embryonic subpallium called the medial ganglionic eminence (MGE). When MGE cells are transplanted into cerebral cortex, these progenitors migrate extensively and differentiate into functional inhibitory neurons. Although MGE progenitors have therapeutic potential following transplantation, it is unknown precisely how these cells distribute within neocortical lamina of the recipient brain. Here we transplanted mouse embryonic day 12.5 MGE progenitors into postnatal neocortex and evaluated laminar distribution of interneuron subtypes using double- and triple-label immunohistochemistry. Studies were performed using wild type (WT) or donor mice lacking a metabotropic GABA(B) receptor subunit (GABA(B1)R KO). MGE-derived neurons from WT and GABA(B1)R KO mice preferentially and densely distributed in neocortical layers 2/3, 5 and 6. As expected, MGE-derived neurons differentiated into parvalbumin+ and somatostatin+ interneurons within these neocortical lamina. Our findings provide insights into the anatomical integration of MGE-derived interneurons following transplantation.

Keywords: GABA; Interneuron; Laminar; Neocortex; Transplantation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Count
  • Embryonic Stem Cells / transplantation*
  • GABAergic Neurons / cytology*
  • GABAergic Neurons / metabolism
  • Interneurons / cytology*
  • Interneurons / metabolism
  • Median Eminence / cytology
  • Mice, Knockout
  • Neocortex / cytology*
  • Neocortex / metabolism
  • Neural Stem Cells / transplantation*
  • Receptors, GABA-B / genetics
  • Receptors, GABA-B / metabolism*

Substances

  • Receptors, GABA-B