Postnatal shifts of interneuron position in the neocortex of normal and reeler mice: evidence for inward radial migration.

During development, interneurons migrate to precise positions in the cortex by tangential and radial migration. The objectives of this study were to characterize the net radial migrations of interneurons during the first postnatal week, and to investigate the role of reelin signaling in regulating those migrations. To observe radial migrations, we compared the laminar positions of interneurons (immunoreactive for GABA or Dlx) in mouse neocortex on postnatal days (P) 0.5 and P7.5. In addition, we used bromodeoxyuridine birthdating to reveal the migrations of different interneuron cohorts. To study the effects of reelin deficiency, experiments were performed in reeler mutant mice. In normal P0.5 cortex, interneurons were most abundant in the marginal zone and layer 5. By P7.5, interneurons were least abundant in the marginal zone, and were distributed more evenly in the cortical plate. This change was attributed mainly to inward migration of middle- to late-born interneurons (produced on embryonic days (E) 13.5 to E16.5) from the marginal zone to layers 2-5. During the same interval, late-born projection neurons (non-immunoreactive for GABA or Dlx) migrated mainly outward, from the intermediate zone to upper cortical layers. In reeler cortex, middle- and late-born interneurons migrated from the superplate on P0.5, to the deep cortical plate on P7.5. Late-born projection neurons in reeler migrated in the opposite direction, from the intermediate zone to the deep cortical plate. We conclude that many middle- and late-born interneurons migrate radially inward, from the marginal zone (or superplate) to the cortical plate, during the first postnatal week in normal and reeler mice. We propose that within the cortical plate, interneuron laminar positions may be determined in part by interactions with projection neurons born on the same day in neurogenesis.