Press Release2022.3.23｜International Institute for Integrative Sleep Medicine (WPI-IIIS)
Dopamine triggers sleep state transitions

Researchers from the University of Tsukuba find a novel neuronalmechanism that initiates rapid-eye movement sleep.
Tsukuba, Japan – historically, the neurological mechanisms
underlying sleep-cycle generation have been elusive. But now, researchers
from Japan have uncovered new information about how the braintransitions from one sleep state to another.
In a study published this month in Science, researchers from theUniversity of Tsukuba have revealed that a temporary increase in
dopamine levels in the basolateral amygdala, a brain region associatedwith emotion, initiates the transition from one sleep state to another.
The sleep cycle includes two different brain states, i.e., non-rapid
eye movement (NREM) and rapid eye movement (REM) sleep, whichalternate during sleep. However, the way in which the brain transitions
from one sleep state to another has not been well defined, something theresearchers at the University of Tsukuba aimed to address.
“Neuroimaging and intracranial recording studies have shown
amygdala activation during REM sleep in humans,” explains lead author of
the study Professor Takeshi Sakurai. “We wanted to examine whether
these changes in amygdala activation, induced by dopamine activity,would correspond to periods of transition between REM sleep and NREM
sleep in mice.”
To do this, the researchers examined changes in extracellular
dopamine levels in mice in several different brain regions that receive
projections from dopamine neurons in the amygdala. They used a finely
tuned dopamine sensor to look for populations of dopamine neurons thatwere activated at specific movements during the sleep/wake cycle.
“The results were surprising,” says senior Professor Sakurai. “Wefound that a transient increase in dopamine in the basolateral amygdalaled to a transition from NREM to REM sleep. Mimicking this dopamine
increase during NREM sleep initiated REM sleep in mice.”
Further, they found that a similar increase in dopamine preceded
cataplexy attacks in narcoleptic mice. Cataplexy is a condition in whichstrong emotions can induce an unexpected transition into REM sleep,
leading to involuntary muscle weakness and altered consciousness.
“Our findings have important implications for understanding
changes in sleep state in both normal and pathological circumstances. For
instance, positive emotions in individuals with cataplexy might lead toincreases dopamine in the amygdala, mimicking the dynamics that trigger
NREM-to-REM transitions,” says Professor Sakurai.
The relationship between sleep state transitions and dopamine
signaling in a brain area associated with emotional processing may haveimportant implications for treating people with cataplexy and narcolepsy.
Further, information about sleep cycle transitions may be useful forunderstanding conditions related to abnormal REM sleep, such as REM
sleep behavior disorder, and diseases involving abnormal DA signaling, suchas Parkinson's disease.

Fig1. Text

Fig1. Changes in dopamine levels in the basolateral nucleus of the amygdala and nucleus
accumbens during the sleep-wake cycle.

Bibliographic information
Hasegawa E, Miyasaka A, Sakurai K, Cherasse Y, Li Y, Sakurai T. (2022) Rapid eye
movement sleep is initiated by basolateral amygdala dopamine signaling in mice.
Science 375(6584), pp. 994-1000
doi: 10.1126/science.abl6618
Media Contact
Alliance and Communication Unit, International Institute for Integrative Sleep Medicine(WPI-IIIS), University of Tsukuba, Japan
E-mail: wpi-iiis-alliance@ml.cc.tsukuba.ac.jp