Progress Report

Elucidation of the mechanism of serotonin over optimism and pessimism1. Serotonin subsystem for optimism and pessimism: observation and measurement

Progress until FY2022

1. Outline of the project

In this research topic, we focus on the dorsal raphe nucleus (DRN), which is the nucleus origin of serotonergic neurons, and the medial prefrontal cortex, orbitofrontal cortex, and amygdala, which are the projection sites of serotonergic neurons. These brain regions are known as the neural substrates that organize action selection and decision-making based on sensory input and are important for generating our mind. We use invasive methods (fiber photometry, fluorescence microscope camera), which are difficult for humans studies, for observation of neural activity in real time during reward acquisition or punishment avoidance behavior.

Our hypotheses: Different neural circuits including serotonin neurons contribute to patience behavior for reward acquisition and punishment avoidance

2. Outcome so far

1.1 Observation of serotonergic activity in the DRN

In this study, we observed serotonin neural activity during mice performing a reward waiting task in which reward probability is changed from 25% to 100%. Serotonin neurons show increased activity during waiting for future reward and phasic increased activity to food presentation. We found that serotonin neural activity during waiting periods are modulated by reward probability. This discovery was made possible by combining the latest experimental techniques with behavioral tasks based on our original hypothesis, and is attracting attention from engineering and medical fields as a new role for serotonin.

1.3 Observation of neural activity in the brain region of serotonin projection

With fluorescence microscope camera, which weighs about 2 g and is attached to mouse's head, we observed hundreds of neural activities in orbitofrontal cortex while the mouse performed the reward waiting task. freely moving animals. Many neurons responded while waiting for delayed reward suggesting that they may be strongly influenced by serotonin input.

3. Future plans

In 1.2, we are working on measurement of extracellular serotonin concentration at serotonin projection sites.
We have completed a unique punishment-avoidance task for this research. From this fiscal year, we will work in parallel with the reward waiting task.

(MIYAZAKI Katsuhiko, MIYAZAKI Kayoko, OIST)