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Molecular and Circuit Architecture of Social Hierarchy

Adam C. Nelson, Vikrant Kapoor, Eric Vaughn, Jeshurun A. Gnanasegaram, Nimrod D. Rubinstein, Venkatesh N Murthy, Catherine Dulac
doi: https://doi.org/10.1101/838664
Adam C. Nelson
Howard Hughes Medical Institute, Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, MA, USA
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Vikrant Kapoor
Howard Hughes Medical Institute, Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, MA, USA
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Eric Vaughn
Howard Hughes Medical Institute, Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, MA, USA
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Jeshurun A. Gnanasegaram
Howard Hughes Medical Institute, Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, MA, USA
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Nimrod D. Rubinstein
Howard Hughes Medical Institute, Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, MA, USACalico Life Sciences LLC, 1170 Veterans Blvd., South San Francisco, USA
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Venkatesh N Murthy
Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, MA, USA
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Catherine Dulac
Howard Hughes Medical Institute, Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, MA, USA
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  • For correspondence: dulac@fas.harvard.edu
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SUMMARY

Social hierarchy is a common organizational structure of animal groups, in which an individual’s social status generates an adaptive behavioral state that facilitates interactions with other group members. Although generally stable, the social status of an animal can change, underscoring the plasticity of the underlying neural circuits. Here, we uncover the molecular and biophysical properties of a cortico-thalamic circuit that supports the emergence of hierarchy in mice. We established a robust behavioral paradigm to explore the establishment of hierarchy among groups of unfamiliar males, and identified the mediodorsal thalamus (MDT) and the caudal part of anterior cingulate area (cACC) as brain areas that are differentially activated between dominants and subordinates. Glutamatergic MDT neurons project to inhibitory parvalbumin interneurons of the cACC, and activity levels of both cell types control competitive performance. Synaptic inputs and excitability of MDT neurons undergo dramatic changes according to the animal social status, and single nucleus sequencing identified increased transcription of the voltage gated ion channel Trpm3 in dominant mice, leading to enhanced excitatory transmission in the MDT-cACC circuit. Our data suggest a model in which cellular, molecular and biophysical plasticity in a thalamocortical circuit controls the expression of social status.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 12, 2019.
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Molecular and Circuit Architecture of Social Hierarchy
Adam C. Nelson, Vikrant Kapoor, Eric Vaughn, Jeshurun A. Gnanasegaram, Nimrod D. Rubinstein, Venkatesh N Murthy, Catherine Dulac
bioRxiv 838664; doi: https://doi.org/10.1101/838664
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Molecular and Circuit Architecture of Social Hierarchy
Adam C. Nelson, Vikrant Kapoor, Eric Vaughn, Jeshurun A. Gnanasegaram, Nimrod D. Rubinstein, Venkatesh N Murthy, Catherine Dulac
bioRxiv 838664; doi: https://doi.org/10.1101/838664

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