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

Darshini Mahadevia, Rinki Saha, Alessia Manganaro, Nao Chuhma, Annette Ziolkowski-Blake, Ashlea A. Morgan, Dani Dumitriu, Stephen Rayport and Mark S. Ansorge ()
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Darshini Mahadevia: Columbia University
Rinki Saha: Columbia University
Alessia Manganaro: Columbia University Irving Medical Center
Nao Chuhma: New York State Psychiatric Institute
Annette Ziolkowski-Blake: New York State Psychiatric Institute
Ashlea A. Morgan: Columbia University
Dani Dumitriu: Columbia University
Stephen Rayport: New York State Psychiatric Institute
Mark S. Ansorge: Columbia University

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-27092-z

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