Grant: Operating Grant

Humans and other primates in particular are capable to rapidly adapt to new situations and learn how to make good choices. This fast and flexible learning is achieved by the interplay of millions of brain cells that are organized in distinct parts of the brain. These cells are not centrally controlled. Rather, brain cells coordinate their contributions to solve a new learning problem indirectly in a decentralized way. But the mechanisms of decentralized coordination have remained a fundamental scientific puzzle. This research proposal aims to solve this puzzle by measuring and manipulating cell activities in the three key brain areas contributing to this fast and flexible learning. One brain area is the hippocampal complex where cells rapidly associate sensory events and contexts with reward when we make choices. Cells in another brain area, the prefrontal cortex, uses the memories from the hippocampal complex to actually make a choice. Cells in a third brain area, the anterior cingulate cortex, track the learning success over longer time scales. These cells evaluate outcomes of a choice based on the history of choices in the immediate past. Such a longer term memory is suited to control the other two areas, preventing them to repeat making a bad choice. Thus, this brain area seems to act like a gate keeper that prevents bad and unimportant memories from the hippocampus to influence a choice in the prefrontal cortex. This outlined scenario predicts a specific sequence of brain cell activities unfolding within and between three brain areas. Understanding this unfolding of coordinated activity is the focus of this grant, aiming to understand why weak linkages of the network causally relate to multiple psychiatric syndromes suffering from Attention Deficits, Motivational Dysfunctions, and severe Affective Imbalances. In summary, this proposal emphasizes a true network approach to understand how fast learning and adaptive behavior is achieved in the brain.