Project/Area Number |
22K15633
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Research Category |
Grant-in-Aid for Early-Career Scientists
|
Allocation Type | Multi-year Fund |
Review Section |
Basic Section 51020:Cognitive and brain science-related
|
Research Institution | Okinawa Institute of Science and Technology Graduate University |
Principal Investigator |
サポン ギデオン 沖縄科学技術大学院大学, 神経生物学研究ユニット, ポストドクトラルスカラー (00837198)
|
Project Period (FY) |
2022-04-01 – 2024-03-31
|
Project Status |
Granted (Fiscal Year 2022)
|
Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
|
Keywords | Acetylcholine / flexibility / Reversal learning / dopamine / acetylcholine |
Outline of Research at the Start |
Searching for an alternative strategy when the outcome of an event changes is essential for survival in a changing environment. However, the neural mechanisms governing behavioral flexibility; the ability to adapt to changes in the outcome of a stimulus, remains unknown. This study aims to reveal neural mechanisms of striatal circuits and neuromodulators which are thought to provide flexible updating of previously learned associations. By clarifying the nature of these circuits for the first time, this study will revise the current understanding of their fundamental functions.
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Outline of Annual Research Achievements |
Adaptive behaviours in stochastic environments are critical for future success and survival. In the natural environment, animals need to typically make decisions in a timely manner, assess outcomes to avoid undesirable ones, and update their choice patterns and behaviour accordingly, to promote flexible responding. A long line of studies showing that lesioning of striatal cholinergic interneurons (which release acetylcholine), and pharmacological manipulation of ACh release impaired behavioural flexibility. Notwithstanding, the precise role of ACh in mediating behavioural switching processes, when conditions demand a shift in response, is lacking. Of important relevance are the processes that regulate and mediate the disengagement of old, invalid information, and the engagement of new, valid information on reinforcement contingencies in the striatum. So far, we have successfully designed a behavioural task using a virtual reality system integrated with 2-photon microscope. Using this, we have also commenced simultaneous imaging of ACh release in striatum while mice are engaged in a task with rule switches. Preliminary results show that dynamic spatiotemporal patterning by ACh is a possible way for contextual responses of cholinergic interneurons to integrate context and reward to facilitate behavioral flexibility.
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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 have successfully developed a virtual reality-response learning task with rule switches to examine flexible responding, when reward location is switched. In addition, we have been able to combine this behavioural task with 2-photon imaging to monitor acetylcholine release in the striatum.
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Strategy for Future Research Activity |
A future goal is to test the hypothesis that there is spatial reorganization of dynamic patterns of ACh in association with reversal learning. We also plan to examine in more detail how ACh modulation mediate the inhibition of old choice patterns during goal-directed learning.
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