Publicly Offered Research
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
We will study the neural mechanisms for how emotional fear responses are controlled when they are innapropriate and how this control is dysregulated in conditions such as post-traumatic stress and anxiety disorders. Specifically we will examine how the brain noradrenaline system is regulated by the medial prefrontal cortex, a brain region important in cognition and emotional control.
Controlling and extinguishing memories of traumatic experiences is critical in the treatment of post-traumatic stress disorder and certain anxiety disorders. Dysregulation of the noradrenaline system occurs in PTSD and anxiety disorder patients, but the underlying mechanisms for this are unclear. In previous research related to this grant we showed that the locus coeruleus (LC), the major source of noradrenaline to the forebrain, contains distinct cell populations that project to the amygdala or medial prefrontal cortex (mPFC). In the last year we've established a retrograde monosynaptic rabies tracing approach in mice and rats to map the brainwide afferent inputs to these cell populations. We've found that both cell populations receive some common inputs, but certain connections are specific. Notably, amygdala projecting LC neurons preferentially receive recurrent inputs from the amygdala while mPFC projecting LC neurons preferentially receive afferents from the mPFC. This shows that recurrent connectivity is an important organizational feature of this modularly organized neuromodulatory system and provides a circuit mechanism for their unique response properties and functionality related to emotional learning and memory. We are now finalizing analysis of how stress alters this connectivity.
令和2年度が最終年度であるため、記入しない。
All 2020 2019
All Journal Article (3 results) (of which Int'l Joint Research: 3 results, Peer Reviewed: 3 results) Presentation (22 results) (of which Int'l Joint Research: 22 results, Invited: 22 results)
Nature Reviews Neuroscience
Volume: 21 Issue: 11 Pages: 644-659
10.1038/s41583-020-0360-9
Nature Neuroscience
Volume: － Issue: 6 Pages: 741-753
10.1038/s41593-020-0625-7
Volume: 22 Issue: 10 Pages: 1586-1597
10.1038/s41593-019-0503-3
