A VTA to basal amygdala dopamine projection contributes to signal salient somatosensory events during fear learning.

SummaryThe amygdala is a brain area critical for the formation of fear memories. However, the nature of the teaching signal(s) that drive plasticity in the amygdala are still under debate. Here, we use optogenetic methods to investigate the contribution of ventral tegmental area (VTA) dopamine neurons to auditory-cued fear learning in male mice. Using antero- and retrograde labeling, we found that a sparse, and relatively evenly distributed population of VTA neurons projects to the basal amygdala (BA). In-vivo optrode recordings in behaving mice showed that many VTA neurons, amongst them putative dopamine neurons, are excited by footshocks, and acquire a response to auditory stimuli during fear learning. Combined cfos imaging and retrograde labeling revealed that a large majority of BA-projectors (> 95%) are dopamine neurons, and that BA-projectors become activated by the tone - footshock pairing of fear learning protocols. Finally, silencing VTA dopamine neurons, or their axon terminals in the BA during the footshock, reduced the strength of fear memory as tested one day later, whereas silencing the VTA - CeA projection had no effect. Thus, VTA dopamine neurons projecting to the BA contribute to fear memory formation, by coding for the saliency of the footshock event and by signaling such events to the basal amygdala.Significance statementPowerful mechanisms of fear learning have evolved in animals and humans to enable survival. During fear conditioning, a sensory cue like a tone (the conditioned stimulus, CS) comes to predict an innately aversive stimulus like a mild footshock (the unconditioned stimulus, US). A brain representation of the US must act as a teaching signal to instruct plasticity of the CS representation in fear-related brain areas. Here we show that dopamine neurons in the VTA that project to the BA, contribute to such a teaching signal for plasticity, thereby facilitating the formation of fear memories. Knowledge about the role of dopamine in aversively motivated plasticity might allow further insights into maladaptive plasticities that underlie anxiety and post-traumatic stress disorders in humans.