Internal medicine

Neuroscience

Calcium imaging

Population

Central nervous system

Midbrain

Biology

Sensory system

Dopaminergic

Cognition

Psychology

Ventral tegmental area

Dopamine

Calcium

Medicine

Environmental health

Nature

There is increased appreciation that dopamine neurons in the midbrain respond not only to reward1 and reward-predicting cues1,2, but also to other variables such as the distance to reward3, movements4–9 and behavioural choices10,11. An important question is how the responses to these diverse variables are organized across the population of dopamine neurons. Whether individual dopamine neurons multiplex several variables, or whether there are subsets of neurons that are specialized in encoding specific behavioural variables remains unclear. This fundamental question has been difficult to resolve because recordings from large populations of individual dopamine neurons have not been performed in a behavioural task with sufficient complexity to examine these diverse variables simultaneously. Here, to address this gap, we used two-photon calcium imaging through an implanted lens to record the activity of more than 300 dopamine neurons from the ventral tegmental area of the mouse midbrain during a complex decision-making task. As mice navigated in a virtual-reality environment, dopamine neurons encoded an array of sensory, motor and cognitive variables. These responses were functionally clustered, such that subpopulations of neurons transmitted information about a subset of behavioural variables, in addition to encoding reward. These functional clusters were spatially organized, with neighbouring neurons more likely to be part of the same cluster. Together with the topography between dopamine neurons and their projections, this specialization and anatomical organization may aid downstream circuits in correctly interpreting the wide range of signals transmitted by dopamine neurons. Two-photon calcium imaging of a large population of dopamine neurons in the ventral tegmental area of mice performing a virtual-reality navigation task reveals the organization principles of the dopamine system.

Specialized coding of sensory, motor and cognitive variables in VTA dopamine neurons