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Activity-dependent regulation of dendritic growth and patterning

Key Points

  • Dendritic morphology is tightly regulated during development and in the adult brain, reflecting its relevance to neuronal function. Both activity-dependent and activity-independent mechanisms participate in the growth and branching of dendrites.

  • In many parts of the nervous system, dendritic arborizations are oriented in specific ways to receive their synaptic inputs. The fact that neurons of the same type bear striking similarities in their morphology, and that this is repeated from animal to animal, indicates that there is a genetic component to the regulation of dendritic morphology.

  • The growth and patterning of dendrites can also be influenced by environmental signals, such as retrograde feedback from their targets and interactions with neighbouring cells of the same kind. Several molecules that mediate these effects have been identified. They include semaphorin 3A, Slit1, Notch and brain-derived neurotrophic factor.

  • In many different species and brain structures, there is a close correlation between the arrival of afferents and dendritic maturation. This effect of afferent fibres occurs at two levels — they influence dendritic growth and regulate dendritic patterning. Similarly, the effects of afferent fibres depend on two factors — the arrival of the afferent axon and its synaptic output. Most studies have focused on the role of synaptic activity on dendritic development.

  • The signalling pathways that are activated in response to synaptic activity to affect dendritic development are not fully understood, but calcium seems to be a crucial messenger. The effects of calcium can be global (for example, stimulating transcription through the activation of calcium/calmodulin-dependent protein kinase IV and cAMP-response-element-binding protein) or local (for example, acting on the cytoskeleton to stabilize growing dendrites). However, our understanding of the role of calcium on dendritic development remains rudimentary, and the signalling pathways that are involved in its effects remain to be precisely identified.

Abstract

One of the most remarkable features of the developing brain is its ability to undergo structural change in response to experience. Among the cellular elements that show this kind of plasticity are dendrites, which are the components that receive and process synaptic information. Recent observations indicate that calcium signalling in neurons can regulate dendritic growth and remodelling by several mechanisms, and these mechanisms are likely to be key mediators of structural plasticity in the developing brain.

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Figure 1: Dendritic arborizations of mature central neurons have distinct morphologies.
Figure 2: Two examples of central neurons that undergo dendritic remodelling to refine their connectivity.
Figure 3: Schematic of mechanisms that might mediate calcium-dependent dendritic growth.
Figure 4: Local elevations in intracellular calcium might contribute to dendritic remodelling in vivo.
Figure 5: Representation of how calcium signals might regulate dendritic growth and patterning during development.

References

  1. Yuste, R. & Tank, D. W. Dendritic integration in mammalian neurons, a century after Cajal. Neuron 16, 701–716 (1996).

    Article  CAS  PubMed  Google Scholar 

  2. Connors, B. W. & Regehr, W. G. Neuronal firing: does function follow form? Curr. Biol. 6, 1560–1562 (1996).

    Article  CAS  PubMed  Google Scholar 

  3. Cline, H. T. Dendritic arbor development and synaptogenesis. Curr. Opin. Neurobiol. 11, 118–126 (2001).

    Article  CAS  PubMed  Google Scholar 

  4. Wong, W. T. & Wong, R. O. L. Changing specificity of neurotransmitter regulation of rapid dendritic remodeling during synaptogenesis. Nature Neurosci. 4, 351–352 (2001).

    Article  CAS  PubMed  Google Scholar 

  5. McAllister, A. K. Cellular and molecular mechanisms of dendritic growth. Cereb. Cortex 10, 963–973 (2000).

    Article  CAS  PubMed  Google Scholar 

  6. Whitford, K. L., Dijkhuizen, P., Polleux, F. & Ghosh, A. Molecular control of cortical dendrite development. Annu. Rev. Neurosci. 25, 127–149 (2002).

    Article  CAS  PubMed  Google Scholar 

  7. Woolsey, T. A. & Van Der Loos, H. The structural organization of layer IV in the somatosensory region (SI) of mouse cerebral cortex. The description of a cortical field composed of discrete cytoarchitectonic units. Brain Res. 17, 205–242 (1970).

    Article  CAS  PubMed  Google Scholar 

  8. Greenough W. T. & Chang, F. L. Dendritic pattern formation involves both oriented regression and oriented growth in barrels of mouse somatosensory cortex. Brain Res. 471, 148–152 (1988).

    Article  CAS  PubMed  Google Scholar 

  9. Malun, D. & Brunjes, P. C. Development of olfactory glomeruli: temporal and spatial interactions between olfactory receptor axons and mitral cells in opossums and rats. J. Comp. Neurol. 368, 1–16 (1996).A detailed anatomical study showing the developmental rearrangement of mitral cell dendrites that contact the olfactory glomeruli. These observations indicate a significant role for dendritic reorganization in the refinement of neuronal connectivity.

    Article  CAS  PubMed  Google Scholar 

  10. Nelson, R., Famiglietti, E. V. Jr & Kolb, H. Intracellular staining reveals different levels of stratification for on- and off-center ganglion cells in cat retina. J. Neurophysiol. 41, 472–483 (1978).

    Article  CAS  PubMed  Google Scholar 

  11. Smith, Z. D. J. & Rubel, E. W. Organization and development of brain stem auditory nuclei of the chicken: dendritic gradients in n. laminaris. J. Comp. Neurol. 186, 213–240 (1979).

    Article  CAS  PubMed  Google Scholar 

  12. Smith, Z. D. J. Organization and development of brain stem auditory nuclei of the chicken: dendritic development in n. laminaris. J. Comp. Neurol. 203, 309–333 (1981).

    Article  CAS  PubMed  Google Scholar 

  13. Montague, P. R. & Friedlander, M. J. Expression of an intrinsic growth strategy by mammalian retinal neurons. Proc. Natl Acad. Sci. USA 86, 7223–7227 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Montague, P. R. & Friedlander, M. J. Morphogenesis and territorial coverage by isolated mammalian retinal ganglion cells. J. Neurosci. 11, 1440–1457 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Threadgill, R., Bobb, K. & Ghosh, A. Regulation of dendritic growth and remodeling by Rho, Rac, and Cdc42. Neuron 19, 625–634 (1997).

    Article  CAS  PubMed  Google Scholar 

  16. Purves, D., Snider, W. D. & Voyvodic, J. T. Trophic regulation of nerve cell morphology and innervation in the autonomic nervous system. Nature 336, 123–128 (1988).

    Article  CAS  PubMed  Google Scholar 

  17. Voyvodic, J. T. Development and regulation of dendrites in the rat superior cervical ganglion. J. Neurosci. 7, 904–912 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Voyvodic, J. T. Peripheral target regulation of dendritic geometry in the rat superior cervical ganglion. J. Neurosci. 9, 1997–2010 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wingate, R. J. & Thompson, I. D. Targeting and activity-related dendritic modification in mammalian retinal ganglion cells. J. Neurosci. 14, 6621–6637 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lom, B. & Cohen-Cory, S. Brain-derived neurotrophic factor differentially regulates retinal ganglion cell dendritic and axonal arborization in vivo. J. Neurosci. 19, 9928–9938 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kirby, M. A. & Chalupa, L. M. Retinal crowding alters the morphology of alpha ganglion cells. J. Comp. Neurol. 251, 532–541 (1986).

    Article  CAS  PubMed  Google Scholar 

  22. Gao, F. B., Brenman, J. E., Jan, L. Y. & Jan, Y. N. Genes regulating dendritic outgrowth, branching, and routing in Drosophila. Genes Dev. 13, 2549–2561 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  24. Jontes, J. D. & Smith, S. J. Filopodia, spines, and the generation of synaptic diversity. Neuron 27, 11–14 (2000).

    Article  CAS  PubMed  Google Scholar 

  25. Polleux, F., Morrow, T. & Ghosh, A. Semaphorin 3A is a chemoattractant for cortical apical dendrites. Nature 404, 567–573 (2000).

    Article  CAS  PubMed  Google Scholar 

  26. Whitford, K. L. et al. Regulation of cortical dendrite development by Slit–Robo interactions. Neuron 33, 47–61 (2002).

    Article  CAS  PubMed  Google Scholar 

  27. Sestan, N., Artavanis-Tsakonas, S. & Rakic, P. Contact-dependent inhibition of cortical neurite growth mediated by notch signaling. Science 286, 741–746 (1999).

    Article  CAS  PubMed  Google Scholar 

  28. Redmond, L., Oh, S. R., Hicks, C., Weinmaster, G. & Ghosh, A. Nuclear Notch1 signaling and the regulation of dendritic development. Nature Neurosci. 3, 30–40 (2000).

    Article  CAS  PubMed  Google Scholar 

  29. McAllister, A. K., Lo, D. C. & Katz, L. C. Neurotrophins regulate dendritic growth in developing visual cortex. Neuron 15, 791–803 (1995).

    Article  CAS  PubMed  Google Scholar 

  30. Rakic, P. & Sidman, R. L. Organization of cerebellar cortex secondary to deficit of granule cells in weaver mutant mice. J. Comp. Neurol. 152, 133–161 (1973).

    Article  CAS  PubMed  Google Scholar 

  31. Rakic, P. Role of cell interactions in development of dendritic patterns. Adv. Neurol. 12, 117–134 (1975).

    CAS  PubMed  Google Scholar 

  32. Mason, C. A., Morrison, M. E., Ward, M. S., Zhang, Q. & Baird, D. H. Axon–target interactions in the developing cerebellum. Perspect. Dev. Neurobiol. 5, 69–82 (1997).

    CAS  PubMed  Google Scholar 

  33. Altman, J. & Anderson, W. J. Experimental reorganization of the cerebellar cortex. I. Morphological effects of elimination of all microneurons with prolonged X-irradiation started at birth. J. Comp. Neurol. 146, 355–406 (1972).

    Article  CAS  PubMed  Google Scholar 

  34. Miller, M. Maturation of rat visual cortex. I. A quantitative study of Golgi-impregnated pyramidal neurons. J. Neurocytol. 10, 859–878 (1981).

    Article  CAS  PubMed  Google Scholar 

  35. Miller, M. & Peters, A. Maturation of rat visual cortex. II. A combined Golgi–electron microscope study of pyramidal neurons. J. Comp. Neurol. 203, 555–573 (1981).

    Article  CAS  PubMed  Google Scholar 

  36. Wu, G. Y., Malinow, R. & Cline, H. T. Maturation of a central glutamatergic synapse. Science 274, 972–976 (1996).

    Article  CAS  PubMed  Google Scholar 

  37. Lund, J. S., Holbach, S. M. & Chung, W. W. Postnatal development of thalamic recipient neurons in the monkey striate cortex: II. Influence of afferent driving on spine acquisition and dendritic growth of layer 4C spiny stellate neurons. J. Comp Neurol. 309, 129–140 (1991).

    Article  CAS  PubMed  Google Scholar 

  38. Tieman, S. B., Zec, N. & Tieman, D. G. Dark rearing fails to affect the basal dendritic fields of layer 3 pyramidal cells in the kitten visual cortex. Brain Res. Dev. Brain Res. 84, 39–45 (1995).

    Article  CAS  PubMed  Google Scholar 

  39. Borges, S. & Berry, M. The effects of dark rearing on the development of the visual cortex of rat. J. Comp. Neurol. 180, 277–300 (1978).

    Article  CAS  PubMed  Google Scholar 

  40. Tieman, S. B. & Hirsch, H. V. Exposure to lines of only one orientation modifies dendritic morphology of cells in the visual cortex of the cat. J. Comp. Neurol. 211, 353–362 (1982).

    Article  CAS  PubMed  Google Scholar 

  41. Coleman, P. D. & Riesen, A. H. Environmental effects on cortical dendritic fields. I. Rearing in the dark. J. Anat. 102, 363–374 (1968).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Wiesel, T. N. & Hubel, D. H. Effects of visual deprivation on morphology and physiology of cells in the cat's lateral geniculate body. J. Neurophysiol. 26, 978–993 (1963).

    Article  CAS  PubMed  Google Scholar 

  43. Greenough, W. T. & Volkmar, F. R. Pattern of dendritic branching in occipital cortex of rats reared in complex environments. Exp. Neurol. 40, 491–504 (1973).

    Article  CAS  PubMed  Google Scholar 

  44. Volkmar, F. R. & Greenough, W. T. Rearing complexity affects branching of dendrites in the visual cortex of the rat. Science 176, 1145–1147 (1972).

    Article  Google Scholar 

  45. Greenough, W.T., Larson, J. R. & Withers, G. S. Effects of unilateral and bilateral training in a reaching task on dendritic branching of neurons in the rat motor-sensory forelimb cortex. Behav. Neural Biol. 44, 301–314 (1985).

    Article  CAS  PubMed  Google Scholar 

  46. Withers, G. S. & Greenough, W. T. Reach training selectively alters dendritic branching in subpopulations of layer 2/3 pyramids in rat motor-somatosensory forelimb cortex. Neuropsychologia 27, 61–69 (1989).

    Article  CAS  PubMed  Google Scholar 

  47. Benes, F. M., Parks, T. N. & Rubel, E. W. Rapid dendritic atrophy following deafferentation: an EM morphometric analysis. Brain Res. 122, 1–13 (1977).

    Article  CAS  PubMed  Google Scholar 

  48. Deitch, J. S. & Rubel, E. W. Afferent influences on brain stem auditory nuclei of the chicken: time course and specificity of dendritic atrophy following deafferentation. J. Comp. Neurol. 229, 66–79 (1984).This study clearly shows that afferent activity maintains dendritic structure in a highly localized manner in an in vivo system.

    Article  CAS  PubMed  Google Scholar 

  49. Purves, D. & Hume, R. I. The relation of postsynaptic geometry to the number of presynaptic axons that innervate autonomic ganglion cells. J. Neurosci. 1, 441–452 (1981).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Kalb, R. G. Regulation of motor neuron dendrite growth by NMDA receptor activation. Development 120, 3063–3071 (1994).

    Article  CAS  PubMed  Google Scholar 

  51. Kleim, J. A. et al. Learning-dependent dendritic hypertrophy of cerebellar stellate cells: plasticity of local circuits. Neurobiol. Learn. Mem. 67, 29–33 (1997).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Kaethner, R. J. & Stuermer, C. A. Dynamics of process formation during differentiation of tectal neurons in embryonic zebrafish. J. Neurobiol. 32, 627–639 (1997).

    Article  CAS  PubMed  Google Scholar 

  54. Rajan, I. & Cline, H. T. Glutamate receptor activity is required for normal development of tectal cell dendrites in vivo. J. Neurosci. 18, 7836–7846 (1998).One of the first studies to provide in vivo evidence that glutamatergic signalling regulates dendritic development.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Sin, W. C., Haas, K., Li, Z., Ruthazer, E. S. & Cline, H. T. Visual stimulation regulates dendritic arborization in vivo by a mechanisms requiring NMDA receptor activation and Rho GTPases. Nature (in the press).This paper uses in vivo time-lapse imaging of dendritic arborizations in the tadpole tectum to show the influence of visual stimulation on dendritic growth rates.

  56. Chavaleyre, V., Moos, F. C. & Desarmenien, M. G. Interplay between presynaptic and postsynaptic activities is required for dendritic plasticity and synaptogenesis in the supraoptic nucleus. J. Neurosci. 22, 265–273 (2002).

    Article  Google Scholar 

  57. Vaughn, J. E. Fine structure of synaptogenesis in the vertebrate central nervous system. Synapse 3, 255–285 (1989).

    Article  CAS  PubMed  Google Scholar 

  58. Lichtman, J. W., Burden, S. J., Culican, S. M. & Wong, R. O. L. in Fundamental Neuroscience (eds Zigmond, M. J., Bloom, F. E., Landis, S. C., Roberts, J. L. & Squire, L. R.) 547–580 (Academic Press, San Diego, 1998).

    Google Scholar 

  59. Wang, G. Y., Liets, L. C. & Chalupa, L. M. Unique functional properties of on and off pathways in the developing mammalian retina. J. Neurosci. 21, 4310–4317 (2001).By combining electrophysiology with morphological analysis, this study shows that the functional refinement of RGC connectivity depends on structural remodelling of the dendritic stratification pattern.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Bodnarenko, S. R. & Chalupa, L. M. Stratification of On and Off ganglion cell dendrites is dependent on glutamate-mediated afferent activity in the developing retina. Nature 364, 144–146 (1993).

    Article  CAS  PubMed  Google Scholar 

  61. Bodnarenko, S. R., Jeyarasasingam, G. & Chalupa, L. M. Development and regulation of dendritic stratification in retinal ganglion cells by glutamate-mediated afferent activity. J. Neurosci. 15, 7037–7045 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Bisti, S., Gargini, C. & Chalupa, L. M. Blockade of glutamate-mediated activity in the developing retina perturbs the functional segregation of ON and OFF pathways. J. Neurosci. 18, 5019–5025 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Wong, R. O. L., Herrmann, K. & Shatz, C. J. Remodeling of retinal ganglion cell dendrites in the absence of action potential activity. J. Neurobiol. 22, 685–697 (1991).

    Article  CAS  PubMed  Google Scholar 

  64. Dalva, M. B., Ghosh, A. & Shatz, C. J. Independent control of dendritic and axonal form in the developing lateral geniculate nucleus. J. Neurosci. 14, 3588–3602 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Schilling, K., Dickinson, M. H., Connor, J. A. & Morgan, J. I. Electrical activity in cerebellar cultures determines Purkinje cell dendritic growth patterns. Neuron 7, 891–902 (1991).

    Article  CAS  PubMed  Google Scholar 

  66. Gray, L., Smith, Z. & Rubel, E. W. Development and experiential changes in dendritic symmetry. Brain Res. 244, 360–364 (1982).

    Article  CAS  PubMed  Google Scholar 

  67. Smith, Z. D., Gray L. & Rubel, E. W. Afferent influences on brainstem auditory nuclei of the chicken: n. laminaris dendritic length following monaural conductive hearing loss. J. Comp. Neurol. 220, 199–205 (1983).

    Article  CAS  PubMed  Google Scholar 

  68. Kossel, A., Lowel, S. & Bolz, J. Relationships between dendritic fields and functional architecture in striate cortex of normal and visually deprived cats. J. Neurosci. 15, 3913–3926 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Harris, R. M. & Woolsey, T. A. Morphology of Golgi-impregnated neurons in mouse cortical barrels following vibrissae damage at different postnatal ages. Brain Res. 161, 143–149 (1979).

    Article  CAS  PubMed  Google Scholar 

  70. Steffen, H. & Van der Loos, H. Early lesions of mouse vibrissal follicles: their influence on dendritic orientation in the cortical barrelfield. Exp. Brain Res. 40, 410–431 (1980).

    Article  Google Scholar 

  71. Katz, L. C. & Constantine-Paton, M. Relationships between segregated afferents and postsynaptic neurones in the optic tectum of three-eyed frogs. J. Neurosci. 8, 3160–3180 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Rubel, E. W., Smith, Z. D. J. & Steward, O. Sprouting in the avian brain stem auditory pathway: dependence on dendritic integrity. J. Comp. Neurol. 202, 397–414 (1981).

    Article  CAS  PubMed  Google Scholar 

  73. Born, D. E., Durham, D. & Rubel, E. W. Afferent influences on brainstem auditory nuclei of the chick: nucleus magnocellularis neuronal activity following cochlea removal. Brain Res. 557, 37–47 (1991).

    Article  CAS  PubMed  Google Scholar 

  74. Spitzer, N. C. Activity-dependent neuronal differentiation prior to synapse formation: the functions of calcium transients. J. Physiol. (Paris) 96, 73–80 (2002).

    Article  CAS  Google Scholar 

  75. Rose, C. R. & Konnerth, A. Stores not just for storage: intracellular calcium release and synaptic plasticity. Neuron 31, 519–522 (2001).

    Article  CAS  PubMed  Google Scholar 

  76. Sabatini, B. L., Maravall, M. & Svoboda, K. Ca2+ signaling in dendritic spines. Curr. Opin. Neurobiol. 11, 349–356 (2001).

    Article  CAS  PubMed  Google Scholar 

  77. Yuste, R. & Bonhoeffer, T. Morphological changes in dendritic spines associated with long-term synaptic plasticity. Annu. Rev. Neurosci. 24, 1071–1089 (2001).

    Article  CAS  PubMed  Google Scholar 

  78. Redmond, L., Kashani, A. & Ghosh, A. Calcium regulation of dendritic growth via CaM kinase IV and CREB-mediated transcription. Neuron 34, 999–1010 (2002).This paper provides evidence that dendritic growth induced by VGCC stimulation of cortical neurons involves activation of a CREB-dependent transcriptional programme.

    Article  CAS  PubMed  Google Scholar 

  79. Lohmann, C., Myhr, K. L. & Wong, R. O. L. Transmitter-evoked local calcium release stabilizes developing dendrites. Nature 418, 177–181 (2002).By combining calcium imaging with morphological analysis in the retina, this study provides evidence that local elevations in dendritic calcium can influence the stability of dendritic branches.

    Article  CAS  PubMed  Google Scholar 

  80. McAllister, A. K., Katz, L. C. & Lo, D. C. Neurotrophin regulation of cortical dendritic growth requires activity. Neuron 17, 1057–1064 (1996).

    Article  CAS  PubMed  Google Scholar 

  81. Shieh, P. B., Hu, S.-C., Bobb, K., Timmusk, T. & Ghosh, A. Identification of a signaling pathway involved in calcium regulation of BDNF expression. Neuron 20, 727–740 (1998).

    Article  CAS  PubMed  Google Scholar 

  82. Tao, X., Finkbeiner, S., Arnold, D. B., Shaywitz, A. J. & Greenberg, M. E. Ca influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism. Neuron 20, 709–726 (1998).

    Article  CAS  PubMed  Google Scholar 

  83. Schwartz, P. M., Borghesani, P. R., Levy, R. L., Pomeroy, S. L. & Segal, R. A. Abnormal cerebellar development and foliation in BDNF−/− mice reveals a role for neurotrophins in CNS patterning. Neuron 19, 269–281 (1997).

    Article  CAS  PubMed  Google Scholar 

  84. Horch, H. W., Krüttgen, A., Portbury, S. D. & Katz, L. C. Destabilization of cortical dendrites and spines by BDNF. Neuron 23, 353–364 (1999).

    Article  CAS  PubMed  Google Scholar 

  85. Mertz, K., Koscheck, T. & Schiling, K. Brain-derived neurotrophic factor modulates dendritic morphology of cerebellar basket and stellate cells: an in vitro study. Neuroscience 97, 303–310 (2000).

    Article  CAS  PubMed  Google Scholar 

  86. Vaillant, A. R. et al. Signaling mechanisms underlying reversible, activity-dependent dendrite formation. Neuron 34, 985–998 (2002).

    Article  CAS  PubMed  Google Scholar 

  87. Berridge, M. J. Neuronal calcium signaling. Neuron 21, 13–26 (1998).

    Article  CAS  PubMed  Google Scholar 

  88. Bootman, M. D, Lipp, P. & Berridge, M. J. The organisation and functions of local Ca2+ signals. J. Cell Sci. 114, 2213–2222 (2001).

    Article  CAS  PubMed  Google Scholar 

  89. Spacek, J. & Harris, K. M. Three-dimensional organization of smooth endoplasmic reticulum in hippocampal CA1 dendrites and dendritic spines of the immature and mature rat. J. Neurosci. 17, 190–203 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Yuste, R., Majewska, A. & Holthoff, K. From form to function: calcium compartmentalization in dendritic spines. Nature Neurosci. 3, 653–659 (2000).

    Article  CAS  PubMed  Google Scholar 

  91. Eilers, J., Plant, T. & Konnerth, A. Localized calcium signalling and neuronal integration in cerebellar Purkinje neurones. Cell Calcium 20, 215–226 (1996).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Chen, B. E. et al. Imaging high-resolution structure of GFP-expressing neurons in neocortex in vivo. Learn. Mem. 7, 433–441 (2000).

    Article  CAS  PubMed  Google Scholar 

  94. Wong, W. T., Faulkner-Jones, B., Sanes, J. R. & Wong, R. O. L. Rapid dendritic remodeling in the developing retina: dependence on neurotransmission and reciprocal regulation by Rac and Rho. J. Neurosci. 20, 5024–5036 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Jontes, J. D., Buchanan, J. & Smith, S. J. Growth cone and dendrite dynamics in zebrafish embryos: early events in synaptogenesis imaged in vivo. Nature Neurosci. 3, 231–237 (2000).

    Article  CAS  PubMed  Google Scholar 

  96. Koizumi, S. et al. Characterization of elementary Ca2+ release signals in NGF-differentiated PC12 cells and hippocampal neurons. Neuron 22, 125–137 (1999).

    Article  CAS  PubMed  Google Scholar 

  97. Kettunen, P. et al. Imaging calcium dynamics in the nervous system by means of ballistic delivery of indicators. J. Neurosci. Methods (in the press).

  98. Friedman, H. V., Bresler, T., Garner, C. C. & Ziv, N. E. Assembly of new individual excitatory synapses: time course and temporal order of synaptic molecule recruitment. Neuron 27, 57–69 (2000).

    Article  CAS  PubMed  Google Scholar 

  99. Wu, G. Y. & Cline, H. T. Stabilization of dendritic arbor structure in vivo by CaMKII. Science 279, 222–226 (1998).

    Article  CAS  PubMed  Google Scholar 

  100. Hall, A. & Nobes, C. D. Rho GTPases: molecular switches that control the organization and dynamics of the actin cytoskeleton. Phil. Trans. R. Soc. Lond. B 29, 965–970 (2000).

    Article  Google Scholar 

  101. Ruchhoeft, M. L., Ohnuma, S., McNeill, L., Holt, C. E. & Harris, W. A. The neuronal architecture of Xenopus retinal ganglion cells is sculpted by rho-family GTPases in vivo. J. Neurosci. 19, 8454–8463 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Li, Z., Van Aelst, L. & Cline, H. T. Rho GTPases regulate distinct aspects of dendritic arbor growth in Xenopus central neurons in vivo. Nature Neurosci. 3, 217–225 (2000).

    Article  CAS  PubMed  Google Scholar 

  103. Nakayama, A. Y., Harms, M. B. & Luo, L. Small GTPases Rac and Rho in the maintenance of dendritic spines and branches in hippocampal pyramidal neurons. J. Neurosci. 20, 5329–5338 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Tashiro, A., Minden, A. & Yuste, R. Regulation of dendritic spine morphology by the Rho family of small GTPases: antagonistic roles of Rac and Rho. Cereb. Cortex 10, 927–938 (2000).

    Article  CAS  PubMed  Google Scholar 

  105. Li, Z., Aizenman, C. D. & Cline, H. T. Regulation of Rho GTPases by crosstalk and neuronal activity in vivo. Neuron 33, 741–750 (2002).

    Article  CAS  PubMed  Google Scholar 

  106. Yin, H. L., Hartwig, J. H., Maruyama, K. & Stossel, T. P. Ca2+ control of actin filament length. Effects of macrophage gelsolin on actin polymerization. J. Biol. Chem. 256, 9693–9697 (1981).

    Article  CAS  PubMed  Google Scholar 

  107. Lu, M., Witke, W., Kwiatkowski, D. J. & Kosik, K. S. Delayed retraction of filopodia in gelsolin null mice. J. Cell Biol. 138, 1279–1287 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Star, E. N., Kwiatkowski, D. J. & Murthy, V. N. Rapid turnover of actin in dendritic spines and its regulation by activity. Nature Neurosci. 5, 239–246 (2002).By using fluorescence recovery methods, this study shows that actin turnover in spines is regulated by NMDA receptor activity. Future studies of this kind, linking neurotransmission to the dynamism of the dendritic cytoskeleton, are needed.

    Article  CAS  PubMed  Google Scholar 

  109. Kinosian, H. J. et al. Ca2+ regulation of gelsolin activity: binding and severing of F-actin. Biophys. J. 75, 3101–3109 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Legrand, C., Ferraz, C., Clavel, M. C. & Rabie, A. Distribution of gelsolin in the retina of the developing rabbit. Cell Tissue Res. 264, 335–338 (1991).

    Article  CAS  PubMed  Google Scholar 

  111. Lee, S. & Kolodziej, P. A. Short stop provides an essential link between F-actin and microtubules during axon extension. Development 129, 1195–1204 (2002).

    Article  CAS  PubMed  Google Scholar 

  112. Wu, G. Y., Deisseroth, K. & Tsien, R. W. Spaced stimuli stabilize MAPK pathway activation and its effects on dendritic morphology. Nature Neurosci. 4, 151–158 (2001).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  114. Lohmann, C. & Wong, R. O. L. Cell-type specific dendritic contacts between retinal ganglion cells during development. J. Neurobiol. 48, 150–162 (2001).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work is supported by grants from the National Institute of Neurological Disorders and Stroke and the March of Dimes Birth Defects Foundation (A.G.), and from the National Institutes of Health and the National Science Foundation (R.O.L.W.).

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Correspondence to Anirvan Ghosh.

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DATABASES

LocusLink

AMPA receptors

BDNF

CaMKII

CaMKIV

CREB

gelsolin

MAPK

nAChRs

NMDA receptors

Notch

Rac

RhoA

Sema3A

Slit1

VGCCs

FURTHER INFORMATION

Encyclopedia of Life Sciences

dendrites

dendritic spines

neural activity and the development of brain circuits

synapses

Glossary

PARALLEL FIBRES

The axons of cerebellar granule cells. Parallel fibres emerge from the molecular layer of the cerebellar cortex towards the periphery, where they extend branches perpendicular to the main axis of Purkinje neurons and form so-called en passant synapses with this cell type.

BARREL

A cylindrical column of neurons that is found in the rodent neocortex. Each barrel receives sensory input from a single whisker follicle, and the topographical organization of the barrels corresponds precisely to the arrangement of whisker follicles on the face.

GLOMERULUS

Axon terminals end in a variety of configurations within the neuropil. The most common is en passant or de passage, in which axons make simple synapses as they pass dendrites or cell bodies. By contrast, some axons end in — or produce strings of — enlargements that are often packed with synaptic vesicles. These glomerular-type endings synapse with large numbers of dendrites and other axons clustered around the glomerular ending.

INNER PLEXIFORM LAYER

The retinal layer that is formed by synaptic contacts between the bipolar, the amacrine and the ganglion cells.

WEAVER

This mouse strain is characterized by cerebellar abnormalities and ataxia, which are associated with a mutation in an inwardly rectifying potassium channel.

REELER

A mutant mouse that is characterized by tremors, dystonia and ataxia. These phenotypes are associated with mutations in a protein known as reelin.

DARK REARING

An experimental condition in which an animal is reared in total darkness so that only endogenous activity is present in the developing visual system.

CLIMBING FIBRES

Cerebellar afferents that arise from the inferior olivary nucleus, each of which forms multiple synapses with a single Purkinje cell.

OCULAR DOMINANCE COLUMNS

In the mature primary visual cortex of mammals, most neurons respond predominantly to visual inputs from one eye or the other. Cells that respond to a given eye are arranged in stripes — the ocular dominance columns — that alternate with stripes of neurons that respond to the other eye.

DOMINANT NEGATIVE

Describes a mutant molecule that can form a heteromeric complex with the normal molecule, knocking out the activity of the entire complex.

BALLISTIC METHOD

A transfection method in which the gene of interest is used to coat gold particles, which are then 'fired' into the biological sample using an air gun.

CAGED CALCIUM

In general terms, a caged molecule is a labile derivative of a biologically active molecule that will break down after appropriate (commonly luminous) stimulation to yield the bioactive compound.

RHO GTPASES

A family of proteins that are related to the product of the Ras oncogene and are involved in controlling the polymerization of actin.

TWO-PHOTON MICROSCOPY

A form of microscopy in which a fluorochrome that would normally be excited by a single photon is stimulated quasi-simultaneously by two photons of lower energy. Under these conditions, fluorescence increases as a function of the square of the light intensity, and decreases approximately as the square of the distance from the focus. Because of this behaviour, only fluorochrome molecules near the plane of focus are excited, greatly reducing light scattering and photodamage of the sample.

FILOPODIA

Long, thin protrusions that are present at the periphery of migrating cells and growth cones. They are largely composed of F-actin bundles.

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Wong, R., Ghosh, A. Activity-dependent regulation of dendritic growth and patterning. Nat Rev Neurosci 3, 803–812 (2002). https://doi.org/10.1038/nrn941

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