A hypothalamic circuit for the circadian control of aggression

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


'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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggression / physiology*
  • Animals
  • Brain Mapping
  • Circadian Rhythm / physiology*
  • Corticosterone / blood
  • Excitatory Postsynaptic Potentials / physiology
  • Hypothalamus / cytology
  • Hypothalamus / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neural Pathways / cytology
  • Neural Pathways / physiology*
  • Optogenetics
  • Paraventricular Hypothalamic Nucleus / cytology
  • Paraventricular Hypothalamic Nucleus / physiology
  • Suprachiasmatic Nucleus / physiology
  • Vasoactive Intestinal Peptide / physiology
  • Ventromedial Hypothalamic Nucleus / cytology
  • Ventromedial Hypothalamic Nucleus / physiology
  • gamma-Aminobutyric Acid / physiology


  • Vasoactive Intestinal Peptide
  • gamma-Aminobutyric Acid
  • Corticosterone