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Interrogating the mouse thalamus to correct human neurodevelopmental disorders

Molecular Psychiatry volume 22, pages 183–191 (2017)Cite this article

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Abstract

While localizing sensory and motor deficits is one of the cornerstones of clinical neurology, behavioral and cognitive deficits in psychiatry remain impervious to this approach. In psychiatry, major challenges include the relative subtlety by which neural circuits are perturbed, and the limited understanding of how basic circuit functions relate to thought and behavior. Neurodevelopmental disorders offer a window to addressing the first challenge given their strong genetic underpinnings, which can be linked to biological mechanisms. Such links have benefited from genetic modeling in the mouse, and in this review we highlight how this small mammal is now allowing us to crack neural circuits as well. We review recent studies of mouse thalamus, discussing how they revealed general principles that may underlie human perception and attention. Controlling the magnitude (gain) of thalamic sensory responses is a mechanism of attention, and the mouse has enabled its functional dissection at an unprecedented resolution. Further, modeling human genetic neurodevelopmental disease in the mouse has shown how diminished thalamic gain control can lead to attention deficits. This breaks new ground in how we untangle the complexity of psychiatric diseases; by making thalamic circuits accessible to mechanistic dissection; the mouse has not only taught us how they fundamentally work, but also how their dysfunction can be precisely mapped onto behavioral and cognitive deficits. Future studies promise even more progress, with the hope that principled targeting of identified thalamic circuits can be uniquely therapeutic.

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Acknowledgements

We thank Dr Laszlo Acsady and Dr Sabine Kastner for their comments. We also thank members of the Halassa lab for constructive discussion and feedback. This work has been funded by grants from the NIH (NIMH, NINDS), Brain and Behavior, Feldstein, Klingestein, Sloan and Simons Foundations.

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Authors and Affiliations

  1. The Neuroscience Institute, New York University School of Medicine, New York, NY, USA

    L I Schmitt & M M Halassa

  2. Department of Neuroscience and Physiology, NYU Langone Medical Center, New York, NY, USA

    L I Schmitt & M M Halassa

  3. Department of Psychiatry, NYU Langone Medical Center, New York, NY, USA

    M M Halassa

  4. Center for Neural Science, New York University, New York, NY, USA

    M M Halassa

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Correspondence to M M Halassa.

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Schmitt, L., Halassa, M. Interrogating the mouse thalamus to correct human neurodevelopmental disorders. Mol Psychiatry 22, 183–191 (2017). https://doi.org/10.1038/mp.2016.183

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