Dynamic features of postnatal subventricular zone cell motility: A two‐photon time‐lapse study

Abstract

Neuroblasts migrate long distances in the postnatal subventricular zone (SVZ) and rostral migratory stream (RMS) to the olfactory bulbs. Many fundamental features of SVZ migration are still poorly understood, and we addressed several important questions using two-photon time-lapse microscopy of brain slices from postnatal and adult eGFP(+) transgenic mice. 1) Longitudinal arrays of neuroblasts, so-called chain migration, have never been dynamically visualized in situ. We found that neuroblasts expressing doublecortin-eGFP (Dcx-eGFP) and glutamic acid decarboxylase-eGFP (Gad-eGFP) remained within arrays, which maintained their shape for many hours, despite the fact that there was a wide variety of movement within arrays. 2) In the dorsal SVZ, neuroblasts migrated rostrocaudally as expected, but migration shifted to dorsoventral orientations throughout ventral regions of the lateral ventricle. 3) Whereas polarized bipolar morphology has been a gold standard for inferring migration in histologic sections, our data indicated that migratory morphology was not predictive of motility. 4) Is there local motility in addition to long distance migration? 5) How fast is SVZ migration? Unexpectedly, one-third of motile neuroblasts moved locally in complex exploratory patterns and at average speeds slower than long distance movement. 6) Finally, we tested, and disproved, the hypothesis that all motile cells in the SVZ express doublecortin, indicating that Dcx is not required for migration of all SVZ cell types. These data show that cell motility in the SVZ and RMS is far more complex then previously thought and involves multiple cell types, behaviors, speeds, and directions.

Long-term in vivo single-cell tracking reveals the switch of migration patterns in adult-born juxtaglomerular cells of the mouse olfactory bulb

“…This differs from what can be inferred from the literature, which postulates that adultborn cells (JGNs as well as GCs) either undergo radial migration only [3,4,9] or first migrate predominantly to the GL before populating the GCL [18]. In contrast to what could be inferred from the in vitro data [15], our results demonstrate a surprisingly vigorous migration of the adult-born JGNs in the GL. Around 40% of adult- born JGNs undergo unidirectional migration without abrupt changes in migration direction, ending up somewhere one-to-two glomeruli away from the initial entry points.…”

“…To get a closer insight into the temporal migration pattern of JGNs, we imaged them every 15 Figure 4G, P ≤ 0.01, Mann-Whitney test), but not maximum ( Figure 4H, P = 0.1, Mann-Whitney test) migration speed decreasing significantly between DPI 8 and DPI 14. At the same time, there was no significant difference in the maximum duration of individual stationary periods ( Figure 4I) as well as the cumulative duration of a stationary phase within the 4-h observation window ( Figure 4J) between the two age groups (P = 0.83 and 0.24, respectively, Mann-Whitney test).…”

“…In the second categorizing method (established by Nam et al [15]), cells were subdivided into "migratory", "exploratory" and "intermediate" according to the ratio of the net to the total distance traversed (migratory: 0.6-1.0; exploratory: 0.0-0.4; intermediate: 0.4-0.6). Out of 213 recorded cells (n = 5 mice), 62.7 ± 3.2% were "migratory", 16.5 ± 3.5% "intermediate" and 20.5 ± 2.4% "exploratory" cells (mean ± SEM, Supplementary information, Figure S3D).…”

“…Dividing neuroblasts undergo tangential migration in the RMS, and then radial migration up into the OB, where they differentiate into two groups of functional interneurons: granule cells (GCs) and juxtaglomerular neurons (JGNs) [3][4][5][6][7][8][9][10]. Whereas the dynamics of SVZ cell migration as well as the tangential migration of neuroblasts in, and their detachment from the RMS, have been studied in much detail [10][11][12][13][14][15][16], little is known about their migratory behavior within the OB.…”

“…Monitoring migration of eGFP-positive neuroblasts in acute brain slices of adult and juvenile mice, Nam et al [15] have shown that in contrast to the majority of neuroblasts in the SVZ and along caudal RMS, which are migratory, more rostral neuroblasts slow down or stop at the edge of the RMS. They concluded that "migration is minimal when cells reach the periglomerular layer (GL) of the OB".…”