A substantial decrease in the number of synapses occurs in the mammalian brain from the late postnatal period until the end of life1,2,3,4,5. Although experience plays an important role in modifying synaptic connectivity6,7,8,9,10,11,12,13,14,15,16,17, its effect on this nearly lifelong synapse loss remains unknown. Here we used transcranial two-photon microscopy to visualize postsynaptic dendritic spines in layer I of the barrel cortex in transgenic mice expressing yellow fluorescent protein. We show that in young adolescent mice, long-term sensory deprivation through whisker trimming prevents net spine loss by preferentially reducing the rate of ongoing spine elimination, not by increasing the rate of spine formation. This effect of deprivation diminishes as animals mature but still persists in adulthood. Restoring sensory experience after adolescent deprivation accelerates spine elimination. Similar to sensory manipulation, the rate of spine elimination decreases after chronic blockade of NMDA (N-methyl-d-aspartate) receptors with the antagonist MK801, and accelerates after drug withdrawal. These studies of spine dynamics in the primary somatosensory cortex suggest that experience plays an important role in the net loss of synapses over most of an animal's lifespan, particularly during adolescence.
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Rakic, P., Bourgeois, J. P., Eckenhoff, M. F., Zecevic, N. & Goldman-Rakic, P. S. Concurrent overproduction of synapses in diverse regions of the primate cerebral cortex. Science 232, 232–235 (1986)
Markus, E. J. & Petit, T. L. Neocortical synaptogenesis, aging, and behaviour: lifespan development in the motor-sensory system of the rat. Exp. Neurol. 96, 262–278 (1987)
Huttenlocher, P. R. & Dabholkar, A. S. Regional differences in synaptogenesis in human cerebral cortex. J. Comp. Neurol. 387, 167–178 (1997)
Grutzendler, J., Kasthuri, N. & Gan, W. B. Long-term dendritic spine stability in the adult cortex. Nature 420, 812–816 (2002)
Zuo, Y., Chang, P., Lin, A. & Gan, W. B. Development of long-term dendritic spine stability in diverse regions of cerebral cortex. Neuron 46, 181–189 (2005)
Shatz, C. J. & Stryker, M. P. Ocular dominance in layer IV of the cat's visual cortex and the effects of monocular deprivation. J. Physiol. (Lond.) 281, 267–283 (1978)
Katz, L. C. & Shatz, C. J. Synaptic activity and the construction of cortical circuits. Science 274, 1133–1138 (1996)
Yuste, R. & Bonhoeffer, T. Morphological changes in dendritic spines associated with long-term synaptic plasticity. Annu. Rev. Neurosci. 24, 1071–1089 (2001)
Bailey, C. H. & Kandel, E. R. Structural changes accompanying memory storage. Annu. Rev. Physiol. 55, 397–426 (1993)
Buonomano, D. V. & Merzenich, M. M. Cortical plasticity: from synapses to maps. Annu. Rev. Neurosci. 21, 149–186 (1998)
Lichtman, J. W. & Colman, H. Synapse elimination and indelible memory. Neuron 25, 269–278 (2000)
Valverde, F. Rate and extent of recovery from dark rearing in the visual cortex of the mouse. Brain Res. 33, 1–11 (1971)
Balice-Gordon, R. J. & Lichtman, J. W. Long-term synapse loss induced by focal blockade of postsynaptic receptors. Nature 372, 519–524 (1994)
Winkelmann, E., Brauer, K. & Klutz, K. Spine density of lamina V pyramidal cells in the visual cortex of laboratory rats after lengthy dark exposure [in German with English abstract]. J. Hirnforsch. 18, 21–28 (1977)
Micheva, K. D. & Beaulieu, C. An anatomical substrate for experience-dependent plasticity of the rat barrel field cortex. Proc. Natl Acad. Sci. USA 92, 11834–11838 (1995)
Matsuzaki, M., Honkura, N., Ellis-Davies, G. C. & Kasai, H. M. Structural basis of long-term potentiation in single dendritic spines. Nature 429, 761–766 (2004)
Grossman, A. W., Churchill, J. D., Bates, K. E., Kleim, J. A. & Greenough, W. T. A brain adaptation view of plasticity: is synaptic plasticity an overly limited concept? Prog. Brain Res. 138, 91–108 (2002)
Yuste, R. & Bonhoeffer, T. Genesis of dendritic spines: insights from ultrastructural and imaging studies. Nature Rev. Neurosci. 5, 24–34 (2004)
Denk, W., Strickler, J. H. & Webb, W. W. Two-photon laser scanning fluorescence microscopy. Science 248, 73–76 (1990)
Ziv, N. E. & Smith, S. J. Evidence for a role of dendritic filopodia in synaptogenesis and spine formation. Neuron 17, 91–102 (1996)
Bock, J. & Braun, K. Blockade of N-methyl-d-aspartate receptor activation suppresses learning-induced synaptic elimination. Proc. Natl Acad. Sci. USA 96, 2485–2490 (1999)
Nicoll, R. A. & Malenka, R. C. Expression mechanisms underlying NMDA receptor-dependent long-term potentiation. Ann. NY Acad. Sci. 868, 515–525 (1999)
Sawtell, N. B. et al. NMDA receptor-dependent ocular dominance plasticity in adult visual cortex. Neuron 38, 977–985 (2003)
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)
Turrigiano, G. G. & Nelson, S. B. Homeostatic plasticity in the developing nervous system. Nature Rev. Neurosci. 5, 97–107 (2004)
Sadaka, Y., Weinfeld, E., Lev, D. L. & White, E. L. Changes in mouse barrel synapses consequent to sensory deprivation from birth. J. Comp. Neurol. 457, 75–86 (2003)
Trachtenberg, J. T. et al. Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex. Nature 420, 788–794 (2002)
Knott, G. W., Quairiaux, C., Genoud, C. & Welker, E. Formation of dendritic spines with GABAergic synapses induced by whisker stimulation in adult mice. Neuron 34, 265–273 (2002)
Changeux, J. P. & Danchin, A. Selective stabilisation of developing synapses as a mechanism for the specification of neuronal networks. Nature 264, 705–712 (1976)
Shi, S. H. et al. Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation. Science 284, 1811–1816 (1999)
We thank N. Kasthuri, W. Thompson and K. Helmin for critical comments on this manuscript. This work was supported by grants from the National Institutes of Health to W.-B.G.
Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.
About this article
Cite this article
Zuo, Y., Yang, G., Kwon, E. et al. Long-term sensory deprivation prevents dendritic spine loss in primary somatosensory cortex. Nature 436, 261–265 (2005) doi:10.1038/nature03715
Progress in Neuro-Psychopharmacology and Biological Psychiatry (2019)
Peeking into the sleeping brain: Using in vivo imaging in rodents to understand the relationship between sleep and cognition
Journal of Neuroscience Methods (2019)
Early-life sleep disruption increases parvalbumin in primary somatosensory cortex and impairs social bonding in prairie voles
Science Advances (2019)
Caspase-2 promotes AMPA receptor internalization and cognitive flexibility via mTORC2-AKT-GSK3β signaling
Nature Communications (2019)