The Reverse Engineering of Tiredness

This discovery leads us one step closer to understanding tiredness and how the brain signals to the body that it’s time to sleep.

Everyone gets tired and sleepy. It’s just the body’s way of telling us we need to rest, or that we’re short on energy and nutrients. It’s normal to feel fatigued or desire sleep at the end of a long day, or when you’re chronically sleep deprived. But according to a new study published in the journal Neuron, the parts of the brain responsible for sleep could also play a role in depression-related sleep disturbances and insomnia.

The scientists focused their research on the dorsal raphe nucleus, a part of the brain that contains dorsal raphe nucleus neurons, or DRNDA neurons. This part of the brain has been linked to sleep cycles but has not yet been studied for how it correlates specifically to sleep.

To determine the DRNDA neuron relation to sleep, they tested activity in the dorsal raphe nucleus. First, they tested it in the presence of salient stimuli (for example, they introduced the lab rats to potential mates). The neurons in this part of the brain were active and firing when salient stimuli were present.

They tested again during the sleep/wake cycle of the lab rats and found that the DRNDA neurons were least active while the rats were sleeping. Neuron activity increased when the rats were waking up. When the scientists stimulated the DRNDA neurons, the rats not only woke up, they actually stayed awake. Conversely, when the DRNDA neurons were silenced chemically, the rats were more prone to sleeping, even in the presence of the stimuli that had woken it up before.

Let’s be clear: this was a study in rats, so further testing is required to determine if this DRNDA neuron activity is also responsible for sleep/wake cycle activity in humans. However, the results of the study indicate that these neurons in the dorsal raphe nucleus do play a role in tiredness and wakefulness. Previous studies have found that people suffering from brain damage in this part of the brain have problems with insomnia and sleep disturbances. For example, patients with Lewy body dementia and multiple systems atrophy have problems with excessive daytime sleepiness due to the damage in their dorsal raphe nucleus.

This discovery leads us one step closer to understanding tiredness and how the brain signals to the body that it’s time to sleep. The more we understand it, the easier it will be to produce therapies that target all forms of sleep disturbances and sleep problems.


1. Cho, Jounhong Ryan, Jennifer B. Treweek, J. Elliott Robinson, Cheng Xiao, Lindsay R. Bremner, Alon Greenbaum, and Viviana Gradinaru. “Dorsal Raphe Dopamine Neurons Modulate Arousal and Promote Wakefulness by Salient Stimuli.” Neuron 94, no. 6 (June 21, 2017): 1205–1219.e8. doi:10.1016/j.neuron.2017.05.020.