2019 Fiscal Year Annual Research Report
WillDynamics of REM sleep and appetite
Publicly Offered Research
| Project Area | Creation and Promotion of the Will-Dynamics |
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| Project/Area Number |
19H05004
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| Research Institution | University of Tsukuba |
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Principal Investigator |
ラザルス ミハエル 筑波大学, 国際統合睡眠医科学研究機構, 准教授 (80469650)
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Keywords | レム睡眠 / 食欲 / 意志動力学 |
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| Outline of Annual Research Achievements |
It is widely accepted that sleep disruption affects metabolism and energy balance, but the neuronal mechanisms linking sleep disruption and obesity are poorly defined. Recent work from our lab suggests a role of neurons in the medial prefrontal cortex (mPFC) in linking REM sleep to appetite for highly palatable food (HPF). REM sleep is a unique phase of sleep in mammals that is characterized by random eye movement and low muscle tone throughout the body. The prefrontal cortex plays a role in judging the palatability of foods through taste, smell and texture. Moreover, persons who are obese tend to have increased activity in the prefrontal cortex when exposed to high calorie foods.
We also discovered that REM sleep is suppressed by activation of REM-active dopaminergic or GABAergic mesopontine neurons, suggesting that these neurons may control the level of REM sleep and/or executive functions during REM sleep. In addition, we found that activation of the GABAergic, but not the dopaminergic, mesopontine neurons strongly induced slow-wave sleep. We continue to elucidate a role of dopaminergic and GABAergic mesopontine neurons in linking REM sleep to HPF consumption.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
We elucidated the precise role of dopamine neurotransmission in mediating food preference based on their nutritional and metabolic impact. This project has revealed important insights implicating dopamine signaling in controlling and mediating metabolic disorders related to sleep alterations.
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| Strategy for Future Research Activity |
Mesopontine GABAergic neurons also show high firing rates during REM sleep and strong c-fos expression, a marker of neuronal activity, during REM sleep recovery after REM sleep deprivation; however, chemogenetic activation of mesopontine GABAergic neurons strongly induces slow-wave sleep while effectively suppressing wakefulness and REM sleep. Thus, the function of REM-active mesopontine GABAergic neurons, like the dopaminergic neurons, is elusive. We will label mesopontine GABAergic neurons with inhibitory and excitatory chemogenetic systems by using viral vectors injected into the mesopontine of vesicular GABA transporter (VGAT)-Cre mice and probe effects of labeled neurons on HPF consumption. We will also use optogenetics for inhibiting GABAergic mesopontine neurons specifically during REM sleep to test their role for HPF consumption. To identify and probe REM-active neurons, we will track the neuronal activity of GABAergic mesopontine neurons by in-vivo electrophysiology to detect the firing rate or fiber endomicroscopy to record Ca transients. In addition, we will utilize functional labeling of neurons with optogenetic or chemogenetic systems by using promoters of synthetic immediate-early genes (e.g. ESARE promoter) to probe mesopontine neurons that are specifically activated during REM sleep rebound after REM sleep deprivation and investigate the role of REM-active neurons in HPF consumption.
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Research Products
(2 results)
