New Pool of Cortical Interneuron Precursors in the Early Postnatal Dorsal White Matter

Abstract

The migration of cortical γ-aminobutyric acidergic interneurons has been extensively studied in rodent embryos, whereas few studies have documented their postnatal migration. Combining in vivo analysis together with time-lapse imaging on cortical slices, we explored the origin and migration of cortical interneurons during the first weeks of postnatal life. Strikingly, we observed that a large pool of GAD65-GFP-positive cells accumulate in the dorsal white matter region during the first postnatal week. Part of these cells divides and expresses the transcription factor paired box 6 indicating the presence of local transient amplifying precursors. The vast majority of these cells are immature interneurons expressing the neuronal marker doublecortin and partly the calcium-binding protein calretinin. Time-lapse imaging reveals that GAD65-GFP-positive neurons migrate from the white matter pool into the overlying anterior cingulate cortex (aCC). Some interneurons in the postnatal aCC express the same immature neuronal markers suggesting ongoing migration of calretinin-positive interneurons. Finally, bromodeoxyuridine incorporation experiments confirm that a small fraction of interneurons located in the aCC are generated during the early postnatal period. These results altogether reveal that at postnatal ages, the dorsal white matter contains a pool of interneuron precursors that divide and migrate into the aCC.

Sculpting Cerebral Cortex with Serotonin in Rodent and Primate

“…In addition, subpopulations of NO+ and reelin+ interneurons also express 5-HT 3A ( [52,55]; Figure 1A). By post-natal stages and decreasing with age, 5-HT 3A is also expressed by young neurons expressing doublecortin and/or calretinin generated in the SVZ and migrating towards the olfactory bulb (rostral medial stream) and various cortical and subcortical regions [90,91]. In addition, we have reported that transient-amplifying precursors located in the white matter ventrally to the anterior cingulate cortex produced neurons destined to populate the anterior cingulate cortex and its vicinity [91].…”

“…In mice, cortical migration is almost completed by P4, and is followed by cortical expansion. However, during the first two post-natal weeks and decreasing with age the SVZ retains the capacity to produce CR+ interneurons contributing to the pools of GABAergic neurons mainly populating lower cortical layers and cingulate cortex [90][91][92]. These events are recapitulated in Figure 3A and B. A-B, Both in human and rodent intense proliferation of neuroepithelium and the formation of the preplate (PP) take place around (E10; GW5) and (E11-E12; GW6-7) respectively.…”

“…For example, 5-HT 1A,F are expressed in neocortical proliferative zones in E14.5 rodent brain [17] and the 5-HT 2B are expressed in the proliferative zones of the human occipital cortex [129] and in all microglial cells [170,171]. The 5-HT 1A,B,D , 5-HT 2A , 5-HT 2C and 5-HT 3A , are expressed in specific subpopulations of post-mitotic neurons [17,88,91,167,168,172,173], whereas the 5-HT 6 is expressed in both migrating interneurons and pyramidal neurons [174,175].…”

Neurons on the Move: Migration and Lamination of Cortical Interneurons

“…Wu et al [20] determined that these cells originated in the GE, and maintained the ability to proliferate after reaching the cortex to produce GABAergic daughter cells. A separate study has identified a pool of proliferating GABAergic precursor cells in the postnatal dorsal white matter [34], and although the authors infer the origin of these cells is the LGE/CGE, this is yet to be determined. The requirement for these proliferating GABAergic intermediate progenitors in the cortex remains unknown; however, they may provide a source of inhibitory cells during the late stages of cortical maturation.…”

Future Perspectives for the Treatment of Neonatal Hypoxic-Ischemic Encephalopathy

“…These cells migrated to the overlying anterior cingulate cortex and expressed the calcium-binding protein calretinin (Riccio et al, 2011), although it is still unknown if a similar population of cortical interneurons is generated during the perinatal period in humans.…”