By: Meenu Johnkutty ’21

If you have ever felt the strong impulse to sleep during a boring lecture or movie, researchers from the University of Tsukuba in Japan can explain why. In their study, published in Nature, the researchers led by Yo Oishi implicated a region of the brain called the nucleus accumbens in the onset of slow wave sleep. The nucleus accumbens is a region in the brain that plays a chief role in managing the reward circuit as it is responsible for the release of serotonin and dopamine, or “happy” hormones, in the brain. Adenosine receptors in this region were specifically targeted since the mechanism by which these receptors induce sleep is largely unknown.

The researchers isolated their research to the nucleus accumbens and conducted a battery of chemogenetic and optogenetic tests. First, they activated the adenosine receptors in this region by injecting clozapine-N-oxide, a ligand that evokes neuronal excitation. Motor activity decreased five hours after administration at 20:00, the beginning of a dark hour period known for high levels of activity and arousal. CNO led to a dose dependent 3h increase in slow wave sleep. EEG recordings showed no differences in normal sleep and the sleep induced by CNO, thus revealing how induced sleep was largely physiological.

The researchers targeted the same adenosine receptors using optogenetic activation. Pulses of blue light targeting this region were sent at a frequency between 1-30 Hz. Latency to sleep, or the measured time between last pulse transmission and the first waves of slow wave sleep recorded on the EEG, was measured. Bilateral stimulation, or the transmission of light to both eyes, at 20 Hz showed the shortest average sleep latency in the mice.

Results from both these experiments reveal how crucial adenosine receptors are in the mechanisms underlying sleep. Since activation of these receptors increased the pressure to sleep in the nucleus accumbens, a region which is associated with pleasure and motivation, the link between boredom and sleep is clear. Interestingly, the caffeine found in coffee blocks adenosine receptors, thus revealing how an arousal effect is produced. Results from this study show great promise in opening avenues of treatment for insomniacs who experience difficulty in sleeping, since targeting these receptors.

References:

1. Y. Oishi, et al., Slow-wave sleep is controlled by a subset of nucleus accumbens core neurons in mice. Nature Communications 8, (2017). doi: 10.1038/s41467-017-00781-4.
2. Image retrieved from: https://www.pexels.com/photo/animal-cat-face-close-up-feline-416160/