A sensory pathway for signaling novel stimuli to dopamine neurons

Dopamine (DA) neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) encode a teaching signal which is causally related to associative learning. DA neurons also respond to salient sensory stimuli, including novel stimuli. These responses are related to stimulus detection and orienting reactions, but they can also promote associative learning. Compared to the role of DA in associative learning, surprisingly little is known about how sensory information is conveyed to DA neurons. In my project, I address this question in mice. First, I will pharmacologically inactivate candidate brain areas which receive olfactory inputs and project to VTA/SNc according to past (orbitofrontal cortex, olfactory tubercle) and unpublished (laterodorsal tegementum and superior colliculus) research, while measuring DA responses to novel and familiar odorants with fiber photometry. The stereotypical sniffing response to novel odors serves as readout of novelty perception. After identifying the brain area(s) necessary for novelty-evoked DA activity, I will use high-density electrophysiology with Neuropixels 2.0 and optogenetic tagging to characterize the pathway in a cell-type specific manner. Finally, I will perform optogenetic manipulations to demonstrate the behavioral relevance of the pathway for learning. Collectively, these results can uncover how salient stimuli activate DA neurons, a fundamental but poorly understood feature of the reward system.