Multi-regional neuronal dynamics of memory-guided flexible behavior

Our brains are able to store information about the world for several seconds after it was acquired, for example the shape and identity of an animal that disappeared behind a tree. Such ‘short-term memory’ is crucial for reasoning and decision-making, providing the link between past events and future behavior. Despite its fundamental importance, how the brain represents and uses short-term memory is not fully understood. One of the challenges is that neural activity representing short-term memory is dispersed across different parts of the brain. Recent technological advances now allow us to measure activity from different regions simultaneously. We propose to study two different behaviors in mice that involve short-term memory. In the first task, a mouse will hear a sound and, after a delay, make a movement to report the sound it heard. The mouse has to maintain information related to the sound during the delay before indicating its decision. In the second task, we will present the mouse with a sound and then deliver another cue that will tell the mouse which actions to choose, contingent on the sound. Here the mouse has to retrieve past sensory information to make a current decision. We will use Neuropixels recording probes and a mesoscale microscope to record activity from hundreds of neurons in the brain. We will sample activity across approximately 50 brain areas, selected based on connectivity data. This data will amount to a map of neural activity underlying short-term memory, decision-making and movement initiation. The activity map will guide the development of computer models of the brain, allowing us to understand general rules of memory-guided decisions.