Abstract
Olfactory bulb interneurons are continuously generated in the subventricular zone (SVZ) and migrate along the rostral migratory stream (RMS) into the olfactory bulb (OB) where the majority becomes local GABAergic interneurons. We previously showed that SVZ-derived progenitor cells expressed glutamic acid decarboxylase 65 kDa (GAD65) very early in the migratory pathway. However, only approximately half of OB GABAergic interneurons use GAD65, an equal number express the 67 kDa GAD enzyme. To investigate the differentiation of these GABAergic interneurons we examined their migration in a transgenic mouse expressing green fluorescent protein (GFP) under the control of the GAD67 promoter. In adult, GFP was expressed by a subpopulation of migratory cells in the SVZ and along the RMS. Using Doublecortin (DCX) as a marker of migrating neuroblasts and bromodeoxyuridine (BrdU) incorporation, we show that these GAD67-GFP neurons co-express DCX and incorporate BrdU indicating they are newly born migratory neuroblasts. This is similar to GAD65 transgene expression, and in contrast to dopaminergic interneuron transgene expression which occurs only after cells reach the olfactory bulb. Although the GAD65/67 transgenes are expressed early in migration, there is minimal protein production in the cells prior to reaching the OB. These results suggest that migrating SVZ-derived neuroblasts acquire GABAergic identity prior to reaching their final location in the olfactory bulb.
References
Altman J, Das GD (1965) Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 124(3):319–335
Altman J, Das GD (1966) Autoradiographic and histological studies of postnatal neurogenesis. I. A longitudinal investigation of the kinetics, migration and transformation of cells incorporating tritiated thymidine in neonate rats, with special reference to postnatal neurogenesis in some brain regions. J Comp Neurol 126(3):337–389
Baker H, Liu N, Chun HS, Saino S, Berlin R, Volpe B, Son JH (2001) Phenotypic differentiation during migration of dopaminergic progenitor cells to the olfactory bulb. J Neurosci 21(21):8505–8513
Carleton A, Petreanu LT, Lansford R, Alvarez-Buylla A, Lledo PM (2003) Becoming a new neuron in the adult olfactory bulb. Nat Neurosci 6(5):507–518
Coskun V, Luskin MB (2001) The expression pattern of the cell cycle inhibitor p19(INK4d) by progenitor cells of the rat embryonic telencephalon and neonatal anterior subventricular zone. J Neurosci 21(9):3092–3103
De Marchis S, Temoney S, Erdelyi F, Bovetti S, Bovolin P, Szabo G, Puche AC (2004) GABAergic phenotypic differentiation of a subpopulation of subventricular derived migrating progenitors. Eur J Neurosci 20(5):1307–1317
del Rio JA, Soriano E (1989) Immunocytochemical detection of 5′-bromodeoxyuridine incorporation in the central nervous system of the mouse. Brain Res Dev Brain Res 49(2):311–317
Faiz M, Acarin L, Villapol S, Schulz S, Castellano B, Gonzalez B (2008) Substantial migration of SVZ cells to the cortex results in the generation of new neurons in the excitotoxically damaged immature rat brain. Mol Cell Neurosci 38(2):170–182
Gleeson JG, Allen KM, Fox JW, Lamperti ED, Berkovic S, Scheffer I, Cooper EC, Dobyns WB, Minnerath SR, Ross ME, Walsh CA (1998) Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein. Cell 92(1):63–72
Goldman SA (1998) Adult neurogenesis: from canaries to the clinic. J Neurobiol 36(2):267–286
Goldman SA, Nottebohm F (1983) Neuronal production, migration, and differentiation in a vocal control nucleus of the adult female canary brain. Proc Natl Acad Sci USA 80(8):2390–2394
Kaplan MS, Hinds JW (1977) Neurogenesis in the adult rat: electron microscopic analysis of light radioautographs. Science 197(4308):1092–1094
Kiyokage E, Pan YZ, Shao Z, Kobayashi K, Szabo G, Yanagawa Y, Obata K, Okano H, Toida K, Puche AC, Shipley MT (2010) Molecular identity of periglomerular and short axon cells. J Neurosci 30(3):1185–1196
Kosaka T, Kosaka K, Heizmann CW, Nagatsu I, Wu JY, Yanaihara N, Hama K (1987) An aspect of the organization of the GABAergic system in the rat main olfactory bulb: laminar distribution of immunohistochemically defined subpopulations of GABAergic neurons. Brain Res 411(2):373–378
Lois C, Alvarez-Buylla A (1993) Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia. Proc Natl Acad Sci USA 90(5):2074–2077
Menezes JR, Smith CM, Nelson KC, Luskin MB (1995) The division of neuronal progenitor cells during migration in the neonatal mammalian forebrain. Mol Cell Neurosci 6(6):496–508
Miller FD, Gauthier-Fisher A (2009) Home at last: neural stem cell niches defined. Cell Stem Cell 4(6):507–510
Mugnaini E, Wouterlood FG, Dahl AL, Oertel WH (1984) Immunocytochemical identification of GABAergic neurons in the main olfactory bulb of the rat. Arch Ital Biol 122(2):83–113
Nacher J, Crespo C, McEwen BS (2001) Doublecortin expression in the adult rat telencephalon. Eur J Neurosci 14(4):629–644
Parrish-Aungst S, Shipley MT, Erdelyi F, Szabo G, Puche AC (2007) Quantitative analysis of neuronal diversity in the mouse olfactory bulb. J Comp Neurol 501(6):825–836
Pencea V, Bingaman KD, Freedman LJ, Luskin MB (2001) Neurogenesis in the subventricular zone and rostral migratory stream of the neonatal and adult primate forebrain. Exp Neurol 172(1):1–16
Petreanu L, Alvarez-Buylla A (2002) Maturation and death of adult-born olfactory bulb granule neurons: role of olfaction. J Neurosci 22(14):6106–6113
Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255(5052):1707–1710
Richards LJ, Kilpatrick TJ, Bartlett PF (1992) De novo generation of neuronal cells from the adult mouse brain. Proc Natl Acad Sci USA 89(18):8591–8595
Soriano E, Del Rio JA, Martinez-Guijarro FJ, Ferrer I, Lopez C (1991) Immunocytochemical detection of 5′-bromodeoxyuridine in fluoro-gold-labeled neurons: a simple technique to combine retrograde axonal tracing and neurogenetic characterization of neurons. J Histochem Cytochem 39(11):1565–1570
Tamamaki N, Yanagawa Y, Tomioka R, Miyazaki J, Obata K, Kaneko T (2003) Green fluorescent protein expression and colocalization with calretinin, parvalbumin, and somatostatin in the GAD67-GFP knock-in mouse. J Comp Neurol 467(1):60–79
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This work was supported by grants from Maryland Stem cell research foundation (MSCRFE-0239 to ACP, 100728-002 to CP).
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Plachez, C., Puche, A.C. Early specification of GAD67 subventricular derived olfactory interneurons. J Mol Hist 43, 215–221 (2012). https://doi.org/10.1007/s10735-012-9394-2
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DOI: https://doi.org/10.1007/s10735-012-9394-2