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Recurrent network activity drives striatal synaptogenesis

A Corrigendum to this article was published on 25 July 2012


Neural activity during development critically shapes postnatal wiring of the mammalian brain. This is best illustrated by the sensory systems, in which the patterned feed-forward excitation provided by sensory organs and experience drives the formation of mature topographic circuits capable of extracting specific features of sensory stimuli1,2. In contrast, little is known about the role of early activity in the development of the basal ganglia, a phylogenetically ancient group of nuclei fundamentally important for complex motor action and reward-based learning3,4. These nuclei lack direct sensory input and are only loosely topographically organized5,6, forming interlocking feed-forward and feed-back inhibitory circuits without laminar structure. Here we use transgenic mice and viral gene transfer methods to modulate neurotransmitter release and neuronal activity in vivo in the developing striatum. We find that the balance of activity between the two inhibitory and antagonist pathways in the striatum regulates excitatory innervation of the basal ganglia during development. These effects indicate that the propagation of activity through a multi-stage network regulates the wiring of the basal ganglia, revealing an important role of positive feedback in driving network maturation.

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Figure 1: Conditional knockout of Slc32a1 from direct or indirect pathway MSNs abolishes GABAergic output.
Figure 2: Conditional knockout of Slc32a1 in direct and indirect pathway MSNs results in opposing changes to excitatory synapse number.
Figure 3: In vivo , developmentally restricted postnatal manipulation of activity in direct and indirect pathway MSNs results in opposing changes to excitatory synapse number.
Figure 4: Corticostriatal activity drives synaptogenesis in MSNs.


  1. Wiesel, T. N. & Hubel, D. H. Single-cell responses in striate cortex of kittens deprived of vision in one eye. J. Neurophysiol. 26, 1003–1017 (1963)

    Article  CAS  Google Scholar 

  2. Smith, G. B., Heynen, A. J. & Bear, M. F. Bidirectional synaptic mechanisms of ocular dominance plasticity in visual cortex. Phil. Trans. R. Soc. B 364, 357–367 (2009)

    Article  Google Scholar 

  3. Stephenson-Jones, M., Samuelsson, E., Ericsson, J., Robertson, B. & Grillner, S. Evolutionary conservation of the basal ganglia as a common vertebrate mechanism for action selection. Curr. Biol. 21, 1081–1091 (2011)

    Article  CAS  Google Scholar 

  4. Yin, H. H. & Knowlton, B. J. The role of the basal ganglia in habit formation. Nature Rev. Neurosci. 7, 464–476 (2006)

    Article  CAS  Google Scholar 

  5. Alexander, G. E., DeLong, M. R. & Strick, P. L. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu. Rev. Neurosci. 9, 357–381 (1986)

    Article  CAS  Google Scholar 

  6. Nambu, A. Somatotopic organization of the primate basal ganglia. Front. Neuroanat. 5, 26 (2011)

    Article  Google Scholar 

  7. Smith, Y., Bevan, M. D., Shink, E. & Bolam, J. P. Microcircuitry of the direct and indirect pathways of the basal ganglia. Neuroscience 86, 353–387 (1998)

    Article  CAS  Google Scholar 

  8. Gerfen, C. R. The neostriatal mosaic: multiple levels of compartmental organization in the basal ganglia. Annu. Rev. Neurosci. 15, 285–320 (1992)

    Article  CAS  Google Scholar 

  9. Albin, R. L., Young, A. B. & Penney, J. B. The functional anatomy of basal ganglia disorders. Trends Neurosci. 12, 366–375 (1989)

    Article  CAS  Google Scholar 

  10. Kelly, R. M. & Strick, P. L. Macro-architecture of basal ganglia loops with the cerebral cortex: use of rabies virus to reveal multisynaptic circuits. Prog. Brain Res. 143, 447–459 (2004)

    Article  Google Scholar 

  11. Alexander, G. E. & Crutcher, M. D. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci. 13, 266–271 (1990)

    Article  CAS  Google Scholar 

  12. Kravitz, A. V. et al. Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry. Nature 466, 622–626 (2010)

    Article  ADS  CAS  Google Scholar 

  13. Ferguson, S. M. et al. Transient neuronal inhibition reveals opposing roles of indirect and direct pathways in sensitization. Nature Neurosci. 14, 22–24 (2011)

    Article  CAS  Google Scholar 

  14. Cho, J. & West, M. O. Distributions of single neurons related to body parts in the lateral striatum of the rat. Brain Res. 756, 241–246 (1997)

    Article  CAS  Google Scholar 

  15. Tong, Q., Ye, C.-P., Jones, J. E., Elmquist, J. K. & Lowell, B. B. Synaptic release of GABA by AgRP neurons is required for normal regulation of energy balance. Nature Neurosci. 11, 998–1000 (2008)

    Article  CAS  Google Scholar 

  16. McIntire, S. L., Reimer, R. J., Schuske, K., Edwards, R. H. & Jorgensen, E. M. Identification and characterization of the vesicular GABA transporter. Nature 389, 870–876 (1997)

    Article  ADS  CAS  Google Scholar 

  17. Wojcik, S. M. et al. A shared vesicular carrier allows synaptic corelease of GABA and glycine. Neuron 50, 575–587 (2006)

    Article  CAS  Google Scholar 

  18. Gong, S. et al. A gene expression atlas of the central nervous system based on bacterial artificial chromosomes. Nature 425, 917–925 (2003)

    Article  ADS  CAS  Google Scholar 

  19. Taverna, S., Ilijic, E. & Surmeier, D. J. Recurrent collateral connections of striatal medium spiny neurons are disrupted in models of Parkinson’s disease. J. Neurosci. 28, 5504–5512 (2008)

    Article  CAS  Google Scholar 

  20. Sohal, V. S., Zhang, F., Yizhar, O. & Deisseroth, K. Parvalbumin neurons and gamma rhythms enhance cortical circuit performance. Nature 459, 698–702 (2009)

    Article  ADS  CAS  Google Scholar 

  21. Nimchinsky, E. A., Sabatini, B. L. & Svoboda, K. Structure and function of dendritic spines. Annu. Rev. Physiol. 64, 313–353 (2002)

    Article  CAS  Google Scholar 

  22. Somogyi, P., Bolam, J. P. & Smith, A. D. Monosynaptic cortical input and local axon collaterals of identified striatonigral neurons. A light and electron microscopic study using the Golgi-peroxidase transport-degeneration procedure. J. Comp. Neurol. 195, 567–584 (1981)

    Article  CAS  Google Scholar 

  23. Tepper, J. M., Sharpe, N. A., Koós, T. Z. & Trent, F. Postnatal development of the rat neostriatum: electrophysiological, light- and electron-microscopic studies. Dev. Neurosci. 20, 125–145 (1998)

    Article  CAS  Google Scholar 

  24. Rogan, S. C. & Roth, B. L. Remote control of neuronal signaling. Pharmacol. Rev. 63, 291–315 (2011)

    Article  CAS  Google Scholar 

  25. Krashes, M. J. et al. Rapid, reversible activation of AgRP neurons drives feeding behavior in mice. J. Clin. Invest. 121, 1424–1428 (2011)

    Article  CAS  Google Scholar 

  26. Kwon, H.-B. & Sabatini, B. L. Glutamate induces de novo growth of functional spines in developing cortex. Nature 474, 100–104 (2011)

    Article  CAS  Google Scholar 

  27. Carter, A. G. & Sabatini, B. L. State-dependent calcium signaling in dendritic spines of striatal medium spiny neurons. Neuron 44, 483–493 (2004)

    Article  CAS  Google Scholar 

  28. Meister, M., Wong, R. O., Baylor, D. A. & Shatz, C. J. Synchronous bursts of action potentials in ganglion cells of the developing mammalian retina. Science 252, 939–943 (1991)

    Article  ADS  CAS  Google Scholar 

  29. Triplett, J. W. et al. Retinal input instructs alignment of visual topographic maps. Cell 139, 175–185 (2009)

    Article  CAS  Google Scholar 

  30. Bi, G. & Poo, M. Synaptic modification by correlated activity: Hebb’s postulate revisited. Annu. Rev. Neurosci. 24, 139–166 (2001)

    Article  CAS  Google Scholar 

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We thank Sabatini laboratory members for comments on the manuscript; B. Roth, K. Deisseroth and M. During for AAV backbones encoding hM4D, ChR2 and Cre, respectively; and C. Gerfen for the Rbp4-Cre mouse line. Confocal imaging was done through the Harvard NeuroDiscovery and Olympus Imaging Centers. This work was supported by grants from NINDS (NS046579, B.L.S); the W.F. Milton Fund Award and the Leonard and Isabelle Goldenson Research Fellowship (Y.K.); and NIH (F31 NS074842) and Shapiro predoctoral fellowship (A.S.).

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Authors and Affiliations



Y.K., A.S. and B.L.S. designed the experiments. Y.K. and A.S. performed experiments and analysed data. C.A.J. assisted in experiments and genotyping. B.B.L. generated the conditional Slc32a1 mouse. Y.K., A.S. and B.L.S. wrote the paper with contributions from C.A.J. and B.B.L.

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Correspondence to Bernardo L. Sabatini.

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The authors declare no competing financial interests.

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Kozorovitskiy, Y., Saunders, A., Johnson, C. et al. Recurrent network activity drives striatal synaptogenesis. Nature 485, 646–650 (2012).

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