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Fine-tuning of pre-balanced excitation and inhibition during auditory cortical development

Nature volume 465, pages 927–931 (2010)Cite this article

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Abstract

Functional receptive fields of neurons in sensory cortices undergo progressive refinement during development1,2,3,4. Such refinement may be attributed to the pruning of non-optimal excitatory inputs, reshaping of the excitatory tuning profile through modifying the strengths of individual inputs, or strengthening of cortical inhibition. These models have not been directly tested because of the technical difficulties in assaying the spatiotemporal patterns of functional synaptic inputs during development. Here we apply in vivo whole-cell voltage-clamp recordings to the recipient layer 4 neurons in the rat primary auditory cortex (A1) to determine the developmental changes in the frequency–intensity tonal receptive fields (TRFs) of their excitatory and inhibitory inputs. Surprisingly, we observe co-tuned excitation and inhibition immediately after the onset of hearing, suggesting that a tripartite thalamocortical circuit with relatively strong feedforward inhibition is formed independently of auditory experience. The frequency ranges of tone-driven excitatory and inhibitory inputs first expand within a few days of the onset of hearing and then persist into adulthood. The latter phase is accompanied by a sharpening of the excitatory but not inhibitory frequency tuning profile, which results in relatively broader inhibitory tuning in adult A1 neurons. Thus the development of cortical synaptic TRFs after the onset of hearing is marked by a slight breakdown of previously formed excitation–inhibition balance. Our results suggest that functional refinement of cortical TRFs does not require a selective pruning of inputs, but may depend more on a fine adjustment of excitatory input strengths.

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Figure 1: The synaptic TRFs shortly after the onset of hearing.
Figure 2: Synaptic TRFs at later developmental stages.
Figure 3: Developmental changes in spectral and temporal patterns of excitatory and inhibitory inputs.
Figure 4: Synaptic mechanisms underlying the developmental refinement of spike TRFs in A1.

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Acknowledgements

We thank J. R. Chan for suggestions. This work was supported by grants to L.I.Z. from the US National Institutes of Health/National Institute on Deafness and Other Communication Disorders (R01DC008983, R21DC008588), the Searle Scholar Program, the Klingenstein Foundation and the David and Lucile Packard Foundation (Packard Fellowships for Science and Engineering). H.W.T. is supported by the US National Institutes of Health (EY018718 and EY019049) and the Karl Kirchgessner Foundation. Z.X. is supported by the National Natural Science Foundation of China (grant numbers 30730039, 30970982 and 30670665).

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Authors and Affiliations

  1. Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA ,

    Yujiao J. Sun, Guangying K. Wu, Bao-hua Liu, Pingyang Li, Mu Zhou, Huizhong W. Tao & Li I. Zhang

  2. Department of Biophysics and Physiology, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA,

    Li I. Zhang

  3. Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA,

    Huizhong W. Tao

  4. Department of Physiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China

    Zhongju Xiao

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Contributions

Y.J.S., G.K.W., P.L. and M.Z. performed the experiments. Y.J.S. and B.-h.L. analysed the data. Z.X., H.W.T. and L.I.Z. designed the experiments and analysis. H.W.T. and L.I.Z. wrote the manuscript.

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Correspondence to Huizhong W. Tao or Li I. Zhang.

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Sun, Y., Wu, G., Liu, Bh. et al. Fine-tuning of pre-balanced excitation and inhibition during auditory cortical development. Nature 465, 927–931 (2010). https://doi.org/10.1038/nature09079

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