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Macroscopic gradients of synaptic excitation and inhibition in the neocortex

Nature Reviews Neuroscience volume 21, pages 169–178 (2020)Cite this article

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Abstract

With advances in connectomics, transcriptome and neurophysiological technologies, the neuroscience of brain-wide neural circuits is poised to take off. A major challenge is to understand how a vast diversity of functions is subserved by parcellated areas of mammalian neocortex composed of repetitions of a canonical local circuit. Areas of the cerebral cortex differ from each other not only in their input–output patterns but also in their biological properties. Recent experimental and theoretical work has revealed that such variations are not random heterogeneities; rather, synaptic excitation and inhibition display systematic macroscopic gradients across the entire cortex, and they are abnormal in mental illness. Quantitative differences along these gradients can lead to qualitatively novel behaviours in non-linear neural dynamical systems, by virtue of a phenomenon mathematically described as bifurcation. The combination of macroscopic gradients and bifurcations, in tandem with biological evolution, development and plasticity, provides a generative mechanism for functional diversity among cortical areas, as a general principle of large-scale cortical organization.

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Fig. 1: Macroscopic gradients of synaptic excitation and bifurcations.
Fig. 2: Timescale hierarchies and their implications for functional connectivity.
Fig. 3: Macroscopic gradients of synaptic inhibition.
Fig. 4: Macroscopic gradients in schizophrenia.
Fig. 5: Two-dimensional gradients of primate cortex.

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Acknowledgements

The author thanks R. Chaudhuri, J. Murray, G.Y. Yang, F. Song, J. Mejias, M. Joglekar, X. Ding, B. Fulcher and V. Zerbi for their contributions and help with figures, and H. Kennedy and D. Bliss for their comments on the manuscript. This work was supported by the US Office of Naval Research (ONR) grant N00014-17-1-2041, US National Institutes of Health (NIH) grant 062349 and the Simons Collaboration on the Global Brain program grant 543057SPI.

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    Xiao-Jing Wang

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Wang, XJ. Macroscopic gradients of synaptic excitation and inhibition in the neocortex. Nat Rev Neurosci 21, 169–178 (2020). https://doi.org/10.1038/s41583-020-0262-x

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