Dendritic development and plasticity of adult-born neurons in the mouse olfactory bulb


The mammalian brain maintains few developmental niches where neurogenesis persists into adulthood. One niche is located in the olfactory system where the olfactory bulb continuously receives functional interneurons. In vivo two-photon microscopy of lentivirus-labeled newborn neurons was used to directly image their development and maintenance in the olfactory bulb. Time-lapse imaging of newborn neurons over several days showed that dendritic formation is highly dynamic with distinct differences between spiny neurons and non-spiny neurons. Once incorporated into the network, adult-born neurons maintain significant levels of structural dynamics. This structural plasticity is local, cumulative and sustained in neurons several months after their integration. Thus, I provide a new experimental system for directly studying the pool of regenerating neurons in the intact mammalian brain and suggest that regenerating neurons form a cellular substrate for continuous wiring plasticity in the olfactory bulb.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Experimental model for in vivo imaging of adult-born neurons.
Figure 2: Large scale changes of newborn PGN dendrites during development.
Figure 3: Dendrites of spiny PGNs are stable but their spines are dynamic.
Figure 4: Dendritic dynamics of adult-born granule cells during development.
Figure 5: Dendritic morphology of adult-born neurons at different durations after virus injection.
Figure 6: Adult-born neurons remain structurally dynamic after incorporation into the network (40–47 d.p.i.).
Figure 7: Stable PGNs and granule cells remain structurally dynamic at 90 d.p.i.
Figure 8: Sensory deprivation does not significantly alter dendritic morphology and dynamics of newborn PGNs during early stages of development.


  1. 1

    Lledo, P.M., Alonso, M. & Grubb, M.S. Adult neurogenesis and functional plasticity in neuronal circuits. Nat. Rev. Neurosci. 7, 179–193 (2006).

    CAS  Article  Google Scholar 

  2. 2

    Ming, G.L. & Song, H. Adult neurogenesis in the mammalian central nervous system. Annu. Rev. Neurosci. 28, 223–250 (2005).

    CAS  Article  Google Scholar 

  3. 3

    Altman, J. Autoradiographic and histological studies of postnatal neurogenesis. IV. Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb. J. Comp. Neurol. 137, 433–457 (1969).

    CAS  Article  Google Scholar 

  4. 4

    Alvarez-Buylla, A. & Garcia-Verdugo, J.M. Neurogenesis in adult subventricular zone. J. Neurosci. 22, 629–634 (2002).

    CAS  Article  Google Scholar 

  5. 5

    Kosaka, K. & Kosaka, T. Synaptic organization of the glomerulus in the main olfactory bulb: compartments of the glomerulus and heterogeneity of the periglomerular cells. Anat. Sci. Int. 80, 80–90 (2005).

    Article  Google Scholar 

  6. 6

    Shepherd, G.M., Chen, W.R. & Greer, C.A. Olfactory Bulb in The Synaptic Organization of the Brain (ed. Shepherd, G.M.) 165–216 (Oxford University Press, New York, 2004).

    Google Scholar 

  7. 7

    Jung, J.C., Mehta, A.D., Aksay, E., Stepnoski, R. & Schnitzer, M.J. In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy. J. Neurophysiol. 92, 3121–3133 (2004).

    Article  Google Scholar 

  8. 8

    Mizrahi, A., Crowley, J.C., Shtoyerman, E. & Katz, L.C. High-resolution in vivo imaging of hippocampal dendrites and spines. J. Neurosci. 24, 3147–3151 (2004).

    CAS  Article  Google Scholar 

  9. 9

    Mizrahi, A. & Katz, L.C. Dendritic stability in the adult olfactory bulb. Nat. Neurosci. 6, 1201–1207 (2003).

    CAS  Article  Google Scholar 

  10. 10

    Rubin, B.D. & Katz, L.C. Optical imaging of odorant representations in the mammalian olfactory bulb. Neuron 23, 499–511 (1999).

    CAS  Article  Google Scholar 

  11. 11

    Wachowiak, M. & Cohen, L.B. Representation of odorants by receptor neuron input to the mouse olfactory bulb. Neuron 32, 723–735 (2001).

    CAS  Article  Google Scholar 

  12. 12

    Davenne, M., Custody, C., Charneau, P. & Lledo, P.M. In vivo imaging of migrating neurons in the Mammalian forebrain. Chem. Senses 30 Suppl 1: i115–i116 (2005).

    Article  Google Scholar 

  13. 13

    Mizrahi, A., Lu, J., Irving, R., Feng, G. & Katz, L.C. In vivo imaging of juxtaglomerular neuron turnover in the mouse olfactory bulb. Proc. Natl. Acad. Sci. USA 103, 1912–1917 (2006).

    CAS  Article  Google Scholar 

  14. 14

    Denk, W., Strickler, J.H. & Webb, W.W. Two-photon laser scanning fluorescence microscopy. Science 248, 73–76 (1990).

    CAS  Article  Google Scholar 

  15. 15

    Petreanu, L. & Alvarez-Buylla, A. Maturation and death of adult-born olfactory bulb granule neurons: role of olfaction. J. Neurosci. 22, 6106–6113 (2002).

    CAS  Article  Google Scholar 

  16. 16

    Carleton, A., Petreanu, L.T., Lansford, R., Alvarez-Buylla, A. & Lledo, P.M. Becoming a new neuron in the adult olfactory bulb. Nat. Neurosci. 6, 507–518 (2003).

    CAS  Article  Google Scholar 

  17. 17

    Lee, W.C. et al. Dynamic remodeling of dendritic arbors in GABAergic interneurons of adult visual cortex. PLoS Biol. 4, e29 (2006).

    Article  Google Scholar 

  18. 18

    Niell, C.M., Meyer, M.P. & Smith, S.J. In vivo imaging of synapse formation on a growing dendritic arbor. Nat. Neurosci. 7, 254–260 (2004).

    CAS  Article  Google Scholar 

  19. 19

    Portera-Cailliau, C., Weimer, R.M., De Paola, V., Caroni, P. & Svoboda, K. Diverse modes of axon elaboration in the developing neocortex. PLoS Biol. 3, e272 (2005).

    Article  Google Scholar 

  20. 20

    London, M. & Hausser, M. Dendritic computation. Annu. Rev. Neurosci. 28, 503–532 (2005).

    CAS  Article  Google Scholar 

  21. 21

    Ziv, N.E. & Smith, S.J. Evidence for a role of dendritic filopodia in synaptogenesis and spine formation. Neuron 17, 91–102 (1996).

    CAS  Article  Google Scholar 

  22. 22

    Dailey, M.E. & Smith, S.J. The dynamics of dendritic structure in developing hippocampal slices. J. Neurosci. 16, 2983–2994 (1996).

    CAS  Article  Google Scholar 

  23. 23

    Maletic-Savatic, M., Malinow, R. & Svoboda, K. Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity. Science 283, 1923–1927 (1999).

    CAS  Article  Google Scholar 

  24. 24

    Cooke, B.M. & Woolley, C.S. Gonadal hormone modulation of dendrites in the mammalian CNS. J. Neurobiol. 64, 34–46 (2005).

    CAS  Article  Google Scholar 

  25. 25

    Gao, F.B., Kohwi, M., Brenman, J.E., Jan, L.Y. & Jan, Y.N. Control of dendritic field formation in Drosophila: the roles of flamingo and competition between homologous neurons. Neuron 28, 91–101 (2000).

    CAS  Article  Google Scholar 

  26. 26

    Jan, Y.N. & Jan, L.Y. The control of dendrite development. Neuron 40, 229–242 (2003).

    CAS  Article  Google Scholar 

  27. 27

    Williams, D.W. & Truman, J.W. Cellular mechanisms of dendrite pruning in Drosophila: insights from in vivo time-lapse of remodeling dendritic arborizing sensory neurons. Development 132, 3631–3642 (2005).

    CAS  Article  Google Scholar 

  28. 28

    Wu, G.Y., Zou, D.J., Rajan, I. & Cline, H. Dendritic dynamics in vivo change during neuronal maturation. J. Neurosci. 19, 4472–4483 (1999).

    CAS  Article  Google Scholar 

  29. 29

    Sin, W.C., Haas, K., Ruthazer, E.S. & Cline, H.T. Dendrite growth increased by visual activity requires NMDA receptor and Rho GTPases. Nature 419, 475–480 (2002).

    CAS  Article  Google Scholar 

  30. 30

    Grutzendler, J., Kasthuri, N. & Gan, W.B. Long-term dendritic spine stability in the adult cortex. Nature 420, 812–816 (2002).

    CAS  Article  Google Scholar 

  31. 31

    Holtmaat, A.J. et al. Transient and persistent dendritic spines in the neocortex in vivo. Neuron 45, 279–291 (2005).

    CAS  Article  Google Scholar 

  32. 32

    Purves, D., Hadley, R.D. & Voyvodic, J.T. Dynamic changes in the dendritic geometry of individual neurons visualized over periods of up to 3 months in the superior cervical ganglion of living mice. J. Neurosci. 6, 1051–1060 (1986).

    CAS  Article  Google Scholar 

  33. 33

    Trachtenberg, J.T. et al. Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex. Nature 420, 788–794 (2002).

    CAS  Article  Google Scholar 

  34. 34

    Zuo, Y., Lin, A., Chang, P. & Gan, W.B. Development of long-term dendritic spine stability in diverse regions of cerebral cortex. Neuron 46, 181–189 (2005).

    CAS  Article  Google Scholar 

  35. 35

    Ailles, L.E. & Naldini, L. HIV-1–derived lentiviral vectors. Curr. Top. Microbiol. Immunol. 261, 31–52 (2002).

    CAS  PubMed  Google Scholar 

  36. 36

    Trono, D. Lentiviral vectors: turning a deadly foe into a therapeutic agent. Gene Ther. 7, 20–23 (2000).

    CAS  Article  Google Scholar 

  37. 37

    Feng, G. et al. Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP. Neuron 28, 41–51 (2000).

    CAS  Article  Google Scholar 

  38. 38

    Dittgen, T. et al. Lentivirus-based genetic manipulations of cortical neurons and their optical and electrophysiological monitoring in vivo. Proc. Natl. Acad. Sci. USA 101, 18206–18211 (2004).

    CAS  Article  Google Scholar 

  39. 39

    Kasthuri, N. & Lichtman, J.W. Structural dynamics of synapses in living animals. Curr. Opin. Neurobiol. 14, 105–111 (2004).

    CAS  Article  Google Scholar 

  40. 40

    Saghatelyan, A. et al. Activity-dependent adjustments of the inhibitory network in the olfactory bulb following early postnatal deprivation. Neuron 46, 103–116 (2005).

    CAS  Article  Google Scholar 

  41. 41

    Burrone, J., O'Byrne, M. & Murthy, V.N. Multiple forms of synaptic plasticity triggered by selective suppression of activity in individual neurons. Nature 420, 414–418 (2002).

    CAS  Article  Google Scholar 

  42. 42

    Katz, L.C. & Shatz, C.J. Synaptic activity and the construction of cortical circuits. Science 274, 1133–1138 (1996).

    CAS  Article  Google Scholar 

  43. 43

    Lledo, P.M. & Saghatelyan, A. Integrating new neurons into the adult olfactory bulb: joining the network, life-death decisions, and the effects of sensory experience. Trends Neurosci. 28, 248–254 (2005).

    CAS  Article  Google Scholar 

  44. 44

    Sawamoto, K. et al. New neurons follow the flow of cerebrospinal fluid in the adult brain. Science 311, 629–632 (2006).

    CAS  Article  Google Scholar 

  45. 45

    Ghashghaei, H.T., Lai, C. & Anton, E.S. Neuronal migration in the adult brain: are we there yet? Nat. Rev. Neurosci. 8, 141–151 (2007).

    CAS  Article  Google Scholar 

  46. 46

    Belluzzi, O., Benedusi, M., Ackman, J. & LoTurco, J.J. Electrophysiological differentiation of new neurons in the olfactory bulb. J. Neurosci. 23, 10411–10418 (2003).

    CAS  Article  Google Scholar 

  47. 47

    Spitzer, N.C. Electrical activity in early neuronal development. Nature 444, 707–712 (2006).

    CAS  Article  Google Scholar 

  48. 48

    Knott, G.W., Holtmaat, A., Wilbrecht, L., Welker, E. & Svoboda, K. Spine growth precedes synapse formation in the adult neocortex in vivo. Nat. Neurosci. 9, 1117–1124 (2006).

    CAS  Article  Google Scholar 

  49. 49

    Bozza, T., Feinstein, P., Zheng, C. & Mombaerts, P. Odorant receptor expression defines functional units in the mouse olfactory system. J. Neurosci. 22, 3033–3043 (2002).

    CAS  Article  Google Scholar 

  50. 50

    Sholl, D.A. Dendritic organization in the neurons of the visual and motor cortices of the cat. J. Anat. 87, 387–406 (1953).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references


I thank Y. Finelt for technical help and P. Mombaerts for the M71-GFP mice. I thank I. Segev, Y. Yarom, S. Wagner, I. Davison and members of my lab for critically reading early versions of the manuscript. Special thanks to S. Wagner for the intracellular labeling of PGNs. A.M. is supported by a Career Development Award from the International Human Frontier Science Program Organization and by ISF grant # 313–05.

Author information



Corresponding author

Correspondence to Adi Mizrahi.

Ethics declarations

Competing interests

The author declares no competing financial interests.

Supplementary information

Supplementary Fig. 1

GFP expressing cells in the OB are neurons, not glia. (PDF 922 kb)

Supplementary Fig. 2

Comparison of labeling patterns of GFP and BrdU. (PDF 1117 kb)

Supplementary Fig. 3

PGN arrival to the glomerular layer decreases with increasing durations after virus injection. (PDF 698 kb)

Supplementary Fig. 4

Morphology of randomly selected PGNs. (PDF 225 kb)

Supplementary Fig. 5

In vivo imaging of adult born PGNs 45 days apart. (PDF 637 kb)

Supplementary Fig. 6

Examples of adult-born PGNs during early development. (PDF 215 kb)

Supplementary Fig. 7

Comparison between in vivo and fixed tissue. (PDF 187 kb)

Supplementary Video 1 (AVI 8230 kb)

Supplementary Video 2 (AVI 1834 kb)

Supplementary Video 3 (AVI 6072 kb)

Supplementary Methods (DOC 40 kb)

Supplementary Text (DOC 36 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Mizrahi, A. Dendritic development and plasticity of adult-born neurons in the mouse olfactory bulb. Nat Neurosci 10, 444–452 (2007).

Download citation

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing