Behavioral orienting but not novelty activates dopamine neurons

Novel stimuli have a profound impact on brain function and behavior. They evoke attention, arousal and sensory exploration and induce synaptic plasticity in brain regions related to learning and memory. Many of these effects have been attributed to novelty-evoked activation of the dopaminergic midbrain and dopamine (DA) release in major projection targets in the striatum. However, it remains controversial if individual DA neurons respond to novel stimuli. To address this question, we recorded and manipulated DA neurons in mice exposed to novel and familiar odors while monitoring orienting behaviors including exploratory sniffing, facial movements, and pupil dilation. We found that DA neurons were activated by orienting behaviors, rather than by novelty itself. Moreover, their activity was causally involved in generating the orienting responses. Finally, we identified a major input region to the dopaminergic midbrain which couples orienting to DA firing. Activity in the mediodorsal pons (mdPons) correlated tightly with sniffing and facial movements. Consequently, optogenetic stimulation of glutamatergic mdPons neurons induced both orienting and DA firing. Our findings suggest that DA neurons do not respond to novelty per se but are activated through descending glutamatergic projections from the mdPons. This mechanism links salient sensory events to DA release, providing a basis for novelty-evoked exploration and plasticity.