The circadian regulation of aggression

A study showed that aggression is influenced by the time of the day in mice.

A paper in Nature Neuroscience described a neural pathway, which exerts circadian regulation of aggression. The idea behind the study is that neurodegenerative diseases often involve the disruption of circadian rhythms and may also be accompanied by aggression. The sundown syndrome illustrates this connection. It affects about 30% of patients with Alzheimer’s disease and many more with other forms of dementia. These patients usually get confused, fatigued, restless and aggressive in the evening.

It is well known that a part of the hypothalamus, the suprachiasmatic nucleus, generates circadian rhythms (this body of work earned the Nobel Prize in Physiology or Medicine in 2017 for Hall, Rosbash and Young). Previous research also established that another part of the hypothalamus (ventrolateral part of the ventromedial nucleus) controls aggression in mice. The researchers activated the neurons of this nucleus by optogenetic stimulation and the mice attacked rival males, females and even inanimate objects.

In the current study, the researchers showed that disrupting the transmission of certain cells of the suprachiasmatic nucleus (the circadian rhythm generator) causes mice to be more aggressive towards an unknown conspecific. Aggression is measured as the time spent biting, chasing, and wrestling the strange mouse placed in the home cage of the subject. Increased aggression manifested in the early hours of the day, as in the evening these mice were only as violent as control mice.  The researchers then showed that the neurons of the suprachiasmatic nucleus send inhibitory projections to the hypothalamic nucleus controlling aggression.

Thus it seems that the suprachiasmatic nucleus inhibits the hypothalamic nucleus and this holds back aggression. The inhibition decreases during the day and thus produces a daily gradient in aggressive behavior in mice. The authors discuss the circuit in more depth and suggest that several other factors may influence its functioning, which may help understanding and treating the sundown syndrome.