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Developmental sensory experience balances cortical excitation and inhibition

Abstract

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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Acknowledgements

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). https://doi.org/10.1038/nature09119

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