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Nat Neurosci. 2018 May;21(5):717-724. doi: 10.1038/s41593-018-0126-0. Epub 2018 Apr 9.

A hypothalamic circuit for the circadian control of aggression.

Author information

1
Department of Neurology, Program in Neuroscience, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
2
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Program in Neuroscience, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
3
Department of Synaptic Transmission in Energy Homeostasis, Max Planck Institute for Metabolism Research, Cologne, Germany.
4
Center for Endocrinology, Diabetes and Preventive Medicine, University Hospital Cologne, Cologne, Germany.
5
Division of Endocrinology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
6
Brain Research Center, College of Life Science, NorthWest University, Xi'an, China.
7
Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
8
Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
9
Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
10
Department of Neurology, Program in Neuroscience, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. csaper@bidmc.harvard.edu.

Abstract

'Sundowning' in dementia and Alzheimer's disease is characterized by early-evening agitation and aggression. While such periodicity suggests a circadian origin, whether the circadian clock directly regulates aggressive behavior is unknown. We demonstrate that a daily rhythm in aggression propensity in male mice is gated by GABAergic subparaventricular zone (SPZGABA) neurons, the major postsynaptic targets of the central circadian clock, the suprachiasmatic nucleus. Optogenetic mapping revealed that SPZGABA neurons receive input from vasoactive intestinal polypeptide suprachiasmatic nucleus neurons and innervate neurons in the ventrolateral part of the ventromedial hypothalamus (VMH), which is known to regulate aggression. Additionally, VMH-projecting dorsal SPZ neurons are more active during early day than early night, and acute chemogenetic inhibition of SPZGABA transmission phase-dependently increases aggression. Finally, SPZGABA-recipient central VMH neurons directly innervate ventrolateral VMH neurons, and activation of this intra-VMH circuit drove attack behavior. Altogether, we reveal a functional polysynaptic circuit by which the suprachiasmatic nucleus clock regulates aggression.

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