We developed a feeding behavioral task in which mice reproduce the food valance change observed in humans, and positive emotion is generated by feeding. We tried to identify the brain regions/neurons that generate positive and negative emotions in response to food valence, and the memory engrams that store food experience in the brain using these tasks. We discovered memory engram neurons that are active after feeding specific foods. Interestingly, we also established an experimental mouse model in which social observation induces feeding behaviors and a food reservation task in which allows us to assess experience-dependent change in the food valence of a regular diet. Additionally, we developed a video task to induce the sensory-specific satiety observed for human brain imaging and performed fMRI analyses.

Identification of Memory Engrams for Food Experience (Mouse research)

We analyzed the areas that increased neural activity after feeding novel food by analyzing neural activity-dependent gene expression. We suggested that food memory engrams are observed in several brain regions. Based on these findings, we performed Ca²⁺ imaging under free-moving conditions using a brain-mounted mini-microscope by expressing calcium indicators in neurons using a virus. We found active neurons after feeding on a specific food. The optogenetic activation of these engram neurons induces seeking behaviors for the particular food. Thus, we are identifying food memory engram neurons.

Mechanism of emotion generation after food experience (mouse research)

To understand the mechanism for the generation of positive emotion by feeding, we established mouse models of a feeding behavioral paradigm in which social observation of the feeding of others affects the feeding. Our findings suggest that social observation of other mice feeding regular food increases the motivation to feed normal food and empathy. This mouse model enables to investigation of the neural mechanisms for psychological induction of feeding behaviors by observation of the feeding of others.

Brain regions that determine food valence (mouse study)

We tried to identify brain regions activated after feeding cheese, sweet chocolate, and bitter chocolate (with high cocoa content), for the first time. We found brain regions that are activated after feeding novel foods, only after feeding a highly palatable food, and only after feeding a less palatable food, respectively. We found that chemogenetic inactivation of the brain region activated following feeding the less palatable food increased the consumption of this less palatable food. Our findings suggested that this brain region plays a central role in the determination of low food valence, thereby suppressing the feeding of the low valued food.

Mechanisms of sensory-specific Satiety in humans and mice

Sensory-specific satiety is a phenomenon in which the food valence is devaluated with eating the same food. We are now identifying the brain regions involved in this sensory-specific satiety in mice. Importantly, we developed a new movie task to induce sensory-specific satiety to perform fMRI brain imaging analysis, for human research. We generated a movie that makes the subjects imagine eating snacks and conducted a questionnaire survey. Our results indicated that only snacks that the subjects imagined themselves eating induced sensory-specific satiety. We performed fMRI analyses in humans using this movie task and identified brain regions activated when sensory-specific satiety is induced.

We are investigating and understanding the biological mechanisms for controlling food valence by identifying memory engrams, and the mechanisms for generating positive emotion induced by various feeding behaviors, such as empathy, following social observation of feeding. Furthermore, we will understand the neural basis of the change in food valence in humans using fMRI and the newly developed movie that induces sensory-specific satiety in humans.