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Developmental sensory experience balances cortical excitation and inhibition


Early in life, neural circuits are highly susceptible to outside influences. The organization of the primary auditory cortex (A1) in particular is governed by acoustic experience during the critical period, an epoch near the beginning of postnatal development throughout which cortical synapses and networks are especially plastic1,2,3,4,5,6,7,8. This neonatal sensitivity to the pattern of sensory inputs is believed to be essential for constructing stable and adequately adapted representations of the auditory world and for the acquisition of language skills by children5,9,10. One important principle of synaptic organization in mature brains is the balance between excitation and inhibition, which controls receptive field structure and spatiotemporal flow of neural activity11,12,13,14,15, but it is unknown how and when this excitatory–inhibitory balance is initially established and calibrated. Here we use whole-cell recording to determine the processes underlying the development of synaptic receptive fields in rat A1. We find that, immediately after the onset of hearing, sensory-evoked excitatory and inhibitory responses are equally strong, although inhibition is less stimulus-selective and mismatched with excitation. However, during the third week of postnatal development, excitation and inhibition become highly correlated. Patterned sensory stimulation drives coordinated synaptic changes across receptive fields, rapidly improves excitatory–inhibitory coupling and prevents further exposure-induced modifications. Thus, the pace of cortical synaptic receptive field development is set by progressive, experience-dependent refinement of intracortical inhibition.

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Figure 1: Refinement of excitatory–inhibitory balance during the A1 critical period.
Figure 2: Delayed maturation of inhibitory frequency tuning.
Figure 3: Patterned stimulation rapidly enhanced excitation and inhibition during P12–P21.
Figure 4: Patterned stimulation improved excitatory–inhibitory coupling by coordinated synaptic modifications across multiple inputs.
Figure 5: Patterned stimulation prevented additional synaptic modifications.

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

    Article  ADS  CAS  Google Scholar 

  2. Miller, K. D. Synaptic economics: competition and cooperation in synaptic plasticity. Neuron 17, 371–374 (1996)

    Article  MathSciNet  CAS  Google Scholar 

  3. Zhang, L. I., Bao, S. & Merzenich, M. M. Persistent and specific influences of early acoustic environments on primary auditory cortex. Nature Neurosci. 4, 1123–1130 (2001)

    Article  CAS  Google Scholar 

  4. Chang, E. F. & Merzenich, M. M. Environmental noise retards auditory cortical development. Science 300, 498–502 (2003)

    Article  ADS  CAS  Google Scholar 

  5. Rubenstein, J. L. & Merzenich, M. M. Model of autism: increased ratio of excitation/inhibition in key neural systems. Genes Brain Behav. 2, 255–267 (2003)

    Article  CAS  Google Scholar 

  6. Hensch, T. K. Critical period plasticity in local cortical circuits. Nature Rev. Neurosci. 6, 877–888 (2005)

    Article  CAS  Google Scholar 

  7. de Villers-Sidani, E., Chang, E. F., Bao, S. & Merzenich, M. M. Critical period for spectral tuning defined in the primary auditory cortex (A1) of the rat. J. Neurosci. 27, 180–189 (2007)

    Article  CAS  Google Scholar 

  8. Huberman, A. D., Feller, M. B. & Chapman, B. Mechanisms underlying development of visual maps and receptive fields. Annu. Rev. Neurosci. 31, 479–509 (2008)

    Article  CAS  Google Scholar 

  9. Doupe, A. J. & Kuhl, P. K. Birdsong and human speech: common themes and mechanisms. Annu. Rev. Neurosci. 22, 567–631 (1999)

    Article  CAS  Google Scholar 

  10. Tallal, P. & Benasich, A. A. Developmental language learning impairments. Dev. Psychopathol. 14, 559–579 (2002)

    Article  Google Scholar 

  11. Shu, Y., Hasenstaub, A. & McCormick, D. A. Turning on and off recurrent balanced cortical activity. Nature 423, 288–293 (2003)

    Article  ADS  CAS  Google Scholar 

  12. Wehr, M. & Zador, A. M. Balanced inhibition underlies tuning and sharpens spike timing in auditory cortex. Nature 426, 442–446 (2003)

    Article  ADS  CAS  Google Scholar 

  13. Tan, A. Y., Zhang, L. I., Merzenich, M. M. & Schreiner, C. E. Tone-evoked excitatory and inhibitory synaptic conductances of primary auditory cortex neurons. J. Neurophysiol. 92, 630–643 (2004)

    Article  Google Scholar 

  14. Froemke, R. C., Merzenich, M. M. & Schreiner, C. E. A synaptic memory trace for cortical receptive field plasticity. Nature 450, 425–429 (2007)

    Article  ADS  CAS  Google Scholar 

  15. Kenet, T., Froemke, R. C., Schreiner, C. E., Pessah, I. N. & Merzenich, M. M. Perinatal exposure to a noncoplanar polychlorinated biphenyl alters tonotopy, receptive fields, and plasticity in rat primary auditory cortex. Proc. Natl Acad. Sci. USA 104, 7646–7651 (2007)

    Article  ADS  CAS  Google Scholar 

  16. Luhmann, H. J. & Prince, D. A. Postnatal maturation of the GABAergic system in rat neocortex. J. Neurophysiol. 65, 247–263 (1991)

    Article  CAS  Google Scholar 

  17. Oswald, A. M. & Reyes, A. Maturation of intrinsic and synaptic properties of layer 2/3 pyramidal neurons in mouse auditory cortex. J. Neurophysiol. 99, 2998–3008 (2008)

    Article  Google Scholar 

  18. Gandhi, S. P., Yanagawa, Y. & Stryker, M. P. Delayed plasticity of inhibitory neurons in developing visual cortex. Proc. Natl Acad. Sci. USA 105, 16797–16802 (2008)

    Article  ADS  CAS  Google Scholar 

  19. Chang, E. F., Bao, S., Imaizumi, K., Schreiner, C. E. & Merzenich, M. M. Development of spectral and temporal response selectivity in the auditory cortex. Proc. Natl Acad. Sci. USA 102, 16460–16465 (2005)

    Article  ADS  CAS  Google Scholar 

  20. Smith, S. L. & Trachtenberg, J. T. Experience-dependent binocular competition in the visual cortex begins at eye opening. Nature Neurosci. 10, 370–375 (2007)

    Article  CAS  Google Scholar 

  21. Stern, E. A., Maravall, M. & Svoboda, K. Rapid development and plasticity of layer 2/3 maps in rat barrel cortex in vivo . Neuron 31, 305–315 (2001)

    Article  CAS  Google Scholar 

  22. Spitzer, N. C. Ion channels in development. Annu. Rev. Neurosci. 2, 363–395 (1979)

    Article  CAS  Google Scholar 

  23. Froemke, R. C., Tsay, I. A., Raad, M., Long, J. D. & Dan, Y. Contribution of individual spikes in burst-induced long-term synaptic modification. J. Neurophysiol. 95, 1620–1629 (2006)

    Article  Google Scholar 

  24. Meliza, C. D. & Dan, Y. Receptive-field modification in rat visual cortex induced by paired visual stimulation and single-cell spiking. Neuron 49, 183–189 (2006)

    Article  CAS  Google Scholar 

  25. Jacob, V., Brasier, D. J., Erchova, I., Feldman, D. & Shulz, D. E. Spike timing-dependent synaptic depression in the in vivo barrel cortex of the rat. J. Neurosci. 27, 1271–1284 (2007)

    Article  CAS  Google Scholar 

  26. Nishiyama, M., Hong, K., Mikoshiba, K., Poo, M. M. & Kato, K. Calcium stores regulate the polarity and input specificity of synaptic modification. Nature 408, 584–588 (2000)

    Article  ADS  CAS  Google Scholar 

  27. Royer, S. & Paré, D. Conservation of total synaptic weight through balanced synaptic depression and potentiation. Nature 422, 518–522 (2003)

    Article  ADS  CAS  Google Scholar 

  28. Lin, Y. et al. Activity-dependent regulation of inhibitory synapse development by Npas4. Nature 455, 1198–1204 (2008)

    Article  ADS  CAS  Google Scholar 

  29. Turrigiano, G. G. & Nelson, S. B. Homeostatic plasticity in the developing nervous system. Nature Rev. Neurosci. 5, 97–107 (2004)

    Article  CAS  Google Scholar 

  30. Sun, Y. J. et al. Fine-tuning of pre-balanced excitation and inhibition during auditory cortical development. Nature 10.1038/nature09079 (this issue)

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We thank C. A. Atencio, T. Babcock, E. Chang, E. de Villers-Sidani, M. R. DeWeese, G. Ehret, S. Gandhi, K. Imaizumi, M. M. Merzenich, C. Niell, A.-M. Oswald, and A. Y. Tan for comments, discussions and technical assistance. This work was supported by the National Institute on Deafness and Other Communication Disorders, the Silvio O. Conte Center for Neuroscience Research at the University of California, San Francisco, Hearing Research Inc. and the John C. and Edward Coleman Fund. R.C.F. is a recipient of a National Institute on Deafness and Other Communication Disorders K99/R00 Career Award, a Jane Coffin Childs Postdoctoral Research Fellowship and a Sandler Translational Research Fellowship. A.J.B. is a recipient of a National Science Foundation Graduate Research Fellowship.

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A.L.D., K.Y., A.J.B. and R.C.F. performed the experiments and analyses. All authors discussed the experiments and contributed to the manuscript.

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Correspondence to Robert C. Froemke.

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The authors declare no competing financial interests.

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Dorrn, A., Yuan, K., Barker, A. et al. Developmental sensory experience balances cortical excitation and inhibition. Nature 465, 932–936 (2010).

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