2017 Fiscal Year Annual Research Report
新規恐怖反応異常マウスで切り拓く恐怖感情と意志力のダイナミクス
Publicly Offered Research
| Project Area | Creation and Promotion of the Will-Dynamics |
|---|
| Project/Area Number |
17H06048
|
|---|
| Research Institution | University of Tsukuba |
|---|
Principal Investigator |
Liu Qinghua 筑波大学, 国際統合睡眠医科学研究機構, 教授 (90723792)
|
|---|
| Project Period (FY) |
2017-04-01 – 2019-03-31
|
| Keywords | 意志力 / 恐怖感情 |
|---|
| Outline of Annual Research Achievements |
High willpower is essential to overcome difficulties. People suffering from anxiety disorders or depression generally exhibit less willpower and low success in life. The molecular and neural mechanism of the willpower is unknown. We developed a forward genetic screen, using a novel predator odor-evoked innate fear assay, to identify ENU-mutagenized mice with abnormal fear behaviors. This fear screen identified a recessive Fear2m/m mutant that exhibited “fearless” phenotype and a dominant Fear1Pop/+ (named Popcorn) mutant pedigree that exhibited excessive “fearful” phenotype in the presence of predator odor. Fear1Pop/+ mutants also exhibited diminished social ranking in the “Tube-test”.
For Fear2m/m mutant, we performed a set of behavior, brain c-fos mapping, tissue lesion, and AAV-fear2 virus injection to rescue fear behavior experiments, and made the novel findings that Fear2 may function as a chemosensor for predator odor, and the trigeminal besides olfactory plays important roles in predator odor-evoked innate fear/defensive behaviors. Our results will be published in Nature Communications (accepted).
For Fear1Pop/+ mutant, we conducted several classical anxiety tests. Fear1Pop/+ mutants exhibited a higher level of anxiety in the tests comparing with their wild-type littermates. We did sleep recording in Fear1Pop/+ mice. Their sleep appeared more fragmented, which is a phenotype often observed in patients with anxiety disorders. We generated Popcorn m/+ mice by CRISPR/Cas9 technology to further verify the causality of the Popcorn mutation for the fearful phenotype
|
| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
We have an excellent research team and received great help from outstanding collaborators.
We collaborated with Dr. Bruce Beutler at UT Southwestern Medical Center, and identified our recessive fearless Fear2m/m mutant mice using his ENU mutant mice generated for his immune screen. We collaborated with Drs. Ko Kobayakawa and Reiko Kobayakawa who are pioneers in the innate fear research, Dr. Takehashi Sakurai who is an outstanding neuroscientist, and made novel findings which will be published in high-profile journal.
Research on Fear1Pop/+ mutant mice had been conducted as in the research proposal.
|
| Strategy for Future Research Activity |
1. To verify the causality of the Popcorn mutation for the “fearful” phenotype in Fear1Pop/+ mice generated by CRISPR/Cas9 technology .
2. To perform other social dominance assays, such as courtship ultrasonic vocalization, territorial urine marking, and food competition to validate Fear1Pop/+ mutant mice exhibit less willpower and diminished social ranking.
3. To examine expression pattern of Popcorn gene in mouse brain by in situ hybridization.
4. To conduct whole brain c-fos mapping to examine where Popcorn may act in the brain, and inject adeno-associated virus (AAV) expressing channelrhodopsin (ChR) into candidate brain regions to examine if optogenetic activation/inhibition of these regions can manipulate fear behavior and willpower in Fear1Pop/+ and wild-type mice.
|
Research Products
(1 results)
