Defining how different types of midbrain dopamine neuron mediate behaviour in the contexts of reward and aversion (360G-Wellcome-109060_Z_15_A)

Learning the value of actions based on prior experience is critical for adaptive behaviour. Rewarding and aversive stimuli have opposite motivational valence, with evidence suggesting that the phasic firing of distinct groups of midbrain dopamine neurons differentially encodes reward and aversion as a function of their projection target. My first research aim is to elucidate the molecular signatures of subpopulations of dopamine neurons innervating the nucleus accumbens or prefrontal cortex. To achieve this, I will combine injections of retrograde tracers with immunofluorescence revelation of molecular markers in mice. My second aim is to determine how distinct types of dopamine neuron, as defined by their specialised molecular profiles and projection targets, encode behaviour. To achieve this, I will carry out recordings of individual molecularly-identified neurons in head-fixed mice as they perform a classical conditioning task incorporating rewarding and aversive events. My third aim it to elucidate a causative role for a specific subpopulation of dopamine neurons in behaviour. To achieve this, I will use an optogenetics-based approach to inhibit these neurons in behaving mice. Overall, this research project is predicted to advance understanding of how different subpopulations of midbrain dopamine neuron subserve behaviour in the context of reward and aversion.