Neural mechanisms underlying behavioral flexibility

2022 Fiscal Year Research-status Report

• Project/Area Number: 22K15633
• 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
• Keywords: Acetylcholine / flexibility

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.

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.

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.

Causes of Carryover

To increase sample size, more mice will be obtained, bred and maintained for colony management. Additional GRIN lenses and implantation kits will be acquired for surgical procedures aimed at inserting GRIN lenses into target brain re
gions. We also plan to purchase immunohistochemical staining reagents for cell-type specific identification of neurons in target brain regions in fixed tissue slices, following recording and analysis.