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Serotonin inputs to the dorsal BNST modulate anxiety in a 5-HT1A receptor-dependent manner

Molecular Psychiatry volume 23, pages 1990–1997 (2018)Cite this article

Abstract

Serotonin (5-HT) neurons project from the raphe nuclei throughout the brain where they act to maintain homeostasis. Here, we study 5-HT inputs into the bed nucleus of the stria terminalis (BNST), a major subdivision of the extended amygdala that has been proposed to regulate responses to anxiogenic environments in humans and rodents. While the dorsal part of the BNST (dBNST) receives dense 5-HT innervation, whether and how 5-HT in the dBNST normally modulates anxiety remains unclear. Using optogenetics, we demonstrate that activation of 5-HT terminals in the dBNST reduces anxiety in a highly anxiogenic environment. Further analysis revealed that optogenetic inhibition of 5-HT inputs into the dBNST increases anxiety in a less anxiogenic environment. We found that 5-HT predominantly hyperpolarizes dBNST neurons, reducing their activity in a manner that can be blocked by a 5-HT1A antagonist. Finally, we demonstrate that activation of 5-HT1A receptors in the dBNST is necessary for the anxiolytic effect observed following optogenetic stimulation of 5-HT inputs into the dBNST. These data reveal that 5-HT release in the dBNST modulates anxiety-like behavior via 5-HT1A receptors under naturalistic conditions.

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Acknowledgments

We thank Thomas Kash, Joshua Gordon and Christoph Kellendonk for comments on previous drafts. We also thank Nilsa Ricci and Ingie Aly for technical assistance. This work was supported by NIMH R01MH091844 and R56MH106809 (to AD), NIMH R01MH105675 and R01MH081968 (to EDL). AGG was supported by a Spain Science Department and a Sackler Institute fellowship; SC was supported by a Brain Behavior Research Foundation (BBRF) Young Investigator Award (grant 21108), a Sackler Foundation fellowship and an NIMH 1K01MH107760; JMS by NIMH F30MH107204; NSB by G12MD007599 and MSA by NIMH R00MH083044 and the Sackler Institute for Developmental Psychobiology.

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  1. Lead Contact.

Authors and Affiliations

  1. Dranovsky-Leonardo (ADL) Lab, Department of Psychiatry, Division of Integrative Neuroscience, Columbia University and the New York State Psychiatric Institute, New York, NY, USA

    A L Garcia-Garcia, A Dranovsky & E D Leonardo

  2. Department of Psychiatry, Columbia University, New York, NY, USA

    S Canetta & M S Ansorge

  3. Department of Psychiatry, Division of Integrative Neuroscience, Columbia University and the New York State Psychiatric Institute, New York, NY, USA

    J M Stujenske

  4. Department of Psychology, Hunter College, City University of New York, New York, NY, USA

    N S Burghardt

Authors
  1. A L Garcia-Garcia
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  2. S Canetta
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  3. J M Stujenske
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  4. N S Burghardt
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  5. M S Ansorge
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  6. A Dranovsky
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  7. E D Leonardo
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Correspondence to A L Garcia-Garcia, A Dranovsky or E D Leonardo.

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Garcia-Garcia, A.L., Canetta, S., Stujenske, J.M. et al. Serotonin inputs to the dorsal BNST modulate anxiety in a 5-HT1A receptor-dependent manner. Mol Psychiatry 23, 1990–1997 (2018). https://doi.org/10.1038/mp.2017.165

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