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Cortical interneurons in autism

Nature Neuroscience volume 24, pages 1648–1659 (2021)Cite this article

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Abstract

The mechanistic underpinnings of autism remain a subject of debate and controversy. Why do individuals with autism share an overlapping set of atypical behaviors and symptoms, despite having different genetic and environmental risk factors? A major challenge in developing new therapies for autism has been the inability to identify convergent neural phenotypes that could explain the common set of symptoms that result in the diagnosis. Although no striking macroscopic neuropathological changes have been identified in autism, there is growing evidence that inhibitory interneurons (INs) play an important role in its neural basis. In this Review, we evaluate and interpret this evidence, focusing on recent findings showing reduced density and activity of the parvalbumin class of INs. We discuss the need for additional studies that investigate how genes and the environment interact to change the developmental trajectory of INs, permanently altering their numbers, connectivity and circuit engagement.

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Fig. 1: Evidence of parvalbumin-expressing cell hypofunction in autism.
Fig. 2: Genes and environment affect milestones of brain development in autism.
Fig. 3: Birth, migration and fate of cortical interneurons.
Fig. 4: Shared phenotypes of parvalbumin cell hypofunction in rodent models of ASD.

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Acknowledgements

This review was inspired by the presentations of experts in the field during a three-day virtual conference entitled Interneurons Dysfunction in Autism held on 16–18 November 2020 (https://sites.google.com/view/interneurons-in-autism-2020/). The keynote speakers were J. Cardin, N. De Marco García, D. Feldman, A. Fenton, G. Fishell, M. Gandal, A. Goel, N. Gouwens, F. Krienen, V. M. Cerdeño, C. McBain and B. Rico. We are grateful to the speakers and all participants for their ideas. We also thank B. Rico, M. Gandal and C. McBain, as well as N. Kourdougli, A. Suresh, S. Sutley and M. Rais for their comments on this manuscript and help with the figures. This research is supported by grant 20160969 from The John Merck Fund to C.P.-C. and A.C., grants R01 HD054453 (National Institute of Child Health and Human Development (NICHD)/National Institutes of Health (NIH)) and R01 NS117597 (National Institute of Mental Health (NIMH)/NIH) and Simons Foundation Autism Research Initiative (SFARI) award no. 513155 to C.P.-C., grants R01 MH099114 (NIMH/NIH), R01 NS105502 (National Institute of Neurological Disorders and Stroke (NINDS)/NIH) and SFARI Pilot Award to A.C., grants W81XWH-17-1-0231 and WX81XWH-18-1-0777 from the US Army Medical Research and Materiel Command (Department of Defense) to A.C. and C.P.-C. and grant W81XWH-15-1-0436 from the Department of Defense to I.M.E.

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  1. Department of Neuroscience Feinberg School of Medicine, Weinberg College of Arts and Sciences, Northwestern University, Chicago, IL, USA

    Anis Contractor

  2. Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Chicago, IL, USA

    Anis Contractor

  3. Division of Biomedical Sciences, UC Riverside School of Medicine, Riverside, CA, USA

    Iryna M. Ethell

  4. Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Carlos Portera-Cailliau

  5. Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Carlos Portera-Cailliau

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Correspondence to Carlos Portera-Cailliau.

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Contractor, A., Ethell, I.M. & Portera-Cailliau, C. Cortical interneurons in autism. Nat Neurosci 24, 1648–1659 (2021). https://doi.org/10.1038/s41593-021-00967-6

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