Learning of spatial values on a cognitive map by the midbrain dopamine system

• Applicant: Dr. Hiroshi Ito
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 505659964

A key feature of the brain is the ability to construct its own internal model to plan an action and predict its subsequent consequences. Spatial navigation is one of such behaviours whereby animals choose a sequence of actions to reach a desired destination that goes beyond the range of sensory perception based on prior knowledge of the environment – so-called cognitive map. While previous studies have elucidated the circuit mechanism to form the brain’s spatial representation of the environment, goal-directed navigation also requires a learning process of spatial values in the environment in order to guide the animal’s decisions of the next navigational destination. Previous studies have suggested a key role for the midbrain dopamine system in such value learning. However, many of these findings are based on a relatively simple behavioural paradigm, in which an animal is required to associate a given stimulus with an appropriate action. It is thus still largely unclear the role of the dopamine system in goal-directed spatial navigation, in which decisions or action initiations are usually self-initiated based on the brain’s cognitive map without relying on external sensory triggers. Therefore, the underlying neural mechanism of spatial-value learning may fundamentally be different from the ones used in stimulus-action association tasks. The main goal of this proposal is to clarify the contribution of the midbrain dopamine system in decisions based on the brain’s internal cognitive map, and to obtain a unified view of the role of the dopamine system in behavioural decisions. To address this question, we will design a new navigation task that allows us to quantify the dynamics of spatial-value estimation, which will be implemented with state-of-the-art technologies, including recording with Neuropixels system together with simultaneous measurement of dopamine release by fibre photometry.Our findings may further lead to a better understanding of Parkinson’s disease that is known to be caused by the loss of dopamine neurons. While patients suffering from Parkinson’s disease have difficulty in initiating self-planned movements including goal-directed spatial navigation, their ability to perform sensory-cue-initiated movements is relatively unaltered. The project will clarify the differential contribution of the midbrain dopamine system between cue-elicited and self-initiated behaviours at the neural-circuit level, providing new insights into not only navigation behaviours but also the pathophysiology of Parkinson's disease.

• DFG Programme: Research Grants