Origin, migration and fate of newly generated neurons in the adult rodent piriform cortex

Abstract

Newly generated neurons are continuously added to the olfactory epithelium and olfactory bulbs of adult mammals. Studies also report newly generated neurons in the piriform cortex, the primary cortical projection site of the olfactory bulbs. The current study used BrdU-injection paradigms, and in vivo and in vitro DiI tracing methods to address three fundamental issues of these cells: their origin, migratory route and fate. The results show that 1 day after a BrdU-injection, BrdU/DCX double-labeled cells appear deep to the ventricular subependyma, within the white matter. Such cells appear further ventral and caudal in the ensuing days, first appearing in the rostral piriform cortex of mice at 2 days after the BrdU-injection, and at 4 days in the rat. In the caudal piriform cortex, BrdU/DCX labeled cells first appear at 4 days after the injection in mice and 7 days in rats. The time it takes for these cells to appear in the piriform cortex and the temporal distribution pattern suggest that they migrate from outside this region. DiI tracing methods confirmed a migratory route to the piriform cortex from the ventricular subependyma. The presence of BrdU/NeuN labeled cells as early as 7 days after a BrdU injection in mice and 10 days in the rat and lasting as long as 41 days indicates that some of these cells have extended survival durations in the adult piriform cortex.

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Acknowledgments

The authors wish to recognize the contribution of Dr. Zhiyin Shan and Matthew Korn for their technical expertise, Dr. Jorge Busciglio and Atul Deshpande for their help with the real-time video microscopy, and Drs. Mark Jacquin, Michael Leon and Richard Robertson for their meaningful discussions regarding these data. We also acknowledge support from NIH grant R01-NS38331 (to CER), NIH training grant T32-NS45540 (for LAS), University of California Discovery Program (for Q-YZ and KN) and an Unrestricted Grant from Research to Prevent Blindness (for EEG).

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Correspondence to Charles E. Ribak.

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24 hr. Fluorescent images of in vitro DiI-labeled cells at 24 hrs after DII implantation of p10 rats. Note the bright bolus of DiI and sparse labeled- cells slightly ventral to the bolus. (TIF 659 kb)

48 hr. Fluorescent images of in vitro DiI-labeled cells at48 hrs after DII implantation of p10 rats. Note the bolus, more labeled cells and further ventral. (TIF 448 kb)

72 hr. Fluorescent images of in vitro DiI-labeled cells at72 hrs after DII implantation of p10 rats. Note the stream of cells emanating along the subcortical white matter. (TIF 434 kb)

96 hr. Fluorescent images of in vitro DiI-labeled cells at 96 hrs after DII implantation of p10 rats. Note the dense numbers of cells, ventral location and widespread distribution in the endopiriform nucleus. Refer them to the figure showing the DCX-labeled cells throughout the endopiriform nucleus. (TIF 460 kb)

Time-lapse confocal microscopy of the piriform cortex 7 days after DiI-implantation. The video encompasses a 14 hour time period. Note that several DiI-labeled cells can be seen to come in and out of the plane of focus of the microscope and DiI-labeled cells can be seen to move ventrally into the piriform cortex. (AVI 63012 kb)

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Shapiro, L.A., Ng, K.L., Kinyamu, R. et al. Origin, migration and fate of newly generated neurons in the adult rodent piriform cortex. Brain Struct Funct 212, 133–148 (2007). https://doi.org/10.1007/s00429-007-0151-3

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Keywords

  • Neurogenesis
  • Olfactory system
  • Doublecortin
  • Bromodeoxyuridine
  • DiI tracing