Neocortical integration of transplanted GABA progenitor cells from wild type and GABAB receptor knockout mouse donors

•Transplantation of MGE progenitor cells into neocortex generates new inhibitory interneurons.•Inhibitory interneurons derived from MGE progenitor cells preferentially distribute in neocortical layers 2/3, 5 and 6.•Functional GABAB receptors are not required for laminar positioning of MGE-derived interneurons following transplantation.

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 GABAB receptor subunit (GABAB1R KO). MGE-derived neurons from WT and GABAB1R 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.