| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2021: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2020: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Outline of Research at the Start |
Sleep is essential but more than 20% of people have an insomnia in Japan. Emotion is one of the main reasons causing sleep problem. However, how emotion change wakefulness is unclear. To clear it, I manipulate CRF neurons in mouse amygdala to confirm the neural circuit and molecular mechanism.
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| Outline of Annual Research Achievements |
The insomnia is a pandemic disease now, and anxiety is though as a main reason. However, the brain areas involved in are unclear. To address it, I used hM3Dq protein to activate corticotropin-releasing factor (CRF) producing neurons in amygdala, which is known to regulate anxiety, and the time in wake increased in these mice. This indicates the amygdala CRF neurons play a role in anxiety-induced wakefulness. However, the neuronal activity of amygdala CRF neurons is opposite to our prediction from wake-promoted by activation of amygdala CRF neurons. Therefore, I categorized the hM3Dq-protein expressed regions. I found out that not only amygdala, but also interstitial nucleus of the posterior limb of the anterior commissure, lateral part (IPACL), which is located in anterior part of amygdala, expressed. To identify the different between IPACL and amygdala, I used in situ hybridization to stain RNA of neurotransmitters expressing in CRF neurons. Dynorphin had low expression in both IPACL and amygdala CRF neurons. Neurotensin had no expression in IPACL and nearly 100% overlapping with amygdala CRF neurons. Both IPACL and amygdala CRF neurons are GABAergic. Based on these, I knockout dynorphin (neurotensin, or CRF) in CRF neurons to further understand the peptide function in wakefulness. My results indicated that knockout of dynorphin in IPACL/amygdala CRF neurons increased the wakefulness compared to control. All my results showed that the regulation of wakefulness in IPACL/amygdala CRF neurons might be caused by dynorphin peptide.
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