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Dopamine promotes aggression in mice via ventral tegmental area to lateral septum projections

Author

Listed:
  • Darshini Mahadevia

    (Columbia University
    New York State Psychiatric Institute)

  • Rinki Saha

    (Columbia University
    New York State Psychiatric Institute)

  • Alessia Manganaro

    (Columbia University Irving Medical Center)

  • Nao Chuhma

    (New York State Psychiatric Institute
    Columbia University)

  • Annette Ziolkowski-Blake

    (New York State Psychiatric Institute)

  • Ashlea A. Morgan

    (Columbia University
    New York State Psychiatric Institute)

  • Dani Dumitriu

    (Columbia University
    Columbia University Irving Medical Center)

  • Stephen Rayport

    (New York State Psychiatric Institute
    Columbia University)

  • Mark S. Ansorge

    (Columbia University
    New York State Psychiatric Institute)

Abstract

Septal-hypothalamic neuronal activity centrally mediates aggressive behavior and dopamine system hyperactivity is associated with elevated aggression. However, the causal role of dopamine in aggression and its target circuit mechanisms are largely unknown. To address this knowledge gap, we studied the modulatory role of the population- and projection-specific dopamine function in a murine model of aggressive behavior. We find that terminal activity of ventral tegmental area (VTA) dopaminergic neurons selectively projecting to the lateral septum (LS) is sufficient for promoting aggression and necessary for establishing baseline aggression. Within the LS, dopamine acts on D2-receptors to inhibit GABAergic neurons, and septal D2-signaling is necessary for VTA dopaminergic activity to promote aggression. Collectively, our data reveal a powerful modulatory influence of dopaminergic synaptic input on LS function and aggression, effectively linking the clinically pertinent hyper-dopaminergic model of aggression with the classic septal-hypothalamic aggression axis.

Suggested Citation

  • Darshini Mahadevia & Rinki Saha & Alessia Manganaro & Nao Chuhma & Annette Ziolkowski-Blake & Ashlea A. Morgan & Dani Dumitriu & Stephen Rayport & Mark S. Ansorge, 2021. "Dopamine promotes aggression in mice via ventral tegmental area to lateral septum projections," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27092-z
    DOI: 10.1038/s41467-021-27092-z
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    References listed on IDEAS

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    1. Sam A. Golden & Mitra Heshmati & Meghan Flanigan & Daniel J. Christoffel & Kevin Guise & Madeline L. Pfau & Hossein Aleyasin & Caroline Menard & Hongxing Zhang & Georgia E. Hodes & Dana Bregman & Lena, 2016. "Basal forebrain projections to the lateral habenula modulate aggression reward," Nature, Nature, vol. 534(7609), pages 688-692, June.
    2. Dayu Lin & Maureen P. Boyle & Piotr Dollar & Hyosang Lee & E. S. Lein & Pietro Perona & David J. Anderson, 2011. "Functional identification of an aggression locus in the mouse hypothalamus," Nature, Nature, vol. 470(7333), pages 221-226, February.
    3. Felix Leroy & Jung Park & Arun Asok & David H. Brann & Torcato Meira & Lara M. Boyle & Eric W. Buss & Eric R. Kandel & Steven A. Siegelbaum, 2018. "A circuit from hippocampal CA2 to lateral septum disinhibits social aggression," Nature, Nature, vol. 564(7735), pages 213-218, December.
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