A VTA to Basal Amygdala Dopamine Projection Contributes to Signal Salient Somatosensory Events during Fear Learning

J Neurosci. 2020 May 13;40(20):3969-3980. doi: 10.1523/JNEUROSCI.1796-19.2020. Epub 2020 Apr 10.


The 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 anterograde 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, among them putative dopamine neurons, are excited by footshocks, and acquire a response to auditory stimuli during fear learning. Combined cfos imaging and retrograde labeling in dopamine transporter (DAT) Cre mice 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 1 d later, whereas silencing the VTA-central amygdala (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 STATEMENT Powerful mechanisms of fear learning have evolved in animals and humans to enable survival. During fear conditioning, a sensory cue, such as a tone (the conditioned stimulus), comes to predict an innately aversive stimulus, such as a mild footshock (the unconditioned stimulus). A brain representation of the unconditioned stimulus must act as a teaching signal to instruct plasticity of the conditioned stimulus representation in fear-related brain areas. Here we show that dopamine neurons in the VTA that project to the basal amygdala 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.

Keywords: VTA; amygdala; auditory conditioning; dopamine; fear memory; optogenetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Amygdala / physiology*
  • Animals
  • Cues
  • Dopamine Plasma Membrane Transport Proteins
  • Dopaminergic Neurons / physiology*
  • Electrophysiological Phenomena / physiology
  • Electroshock
  • Evoked Potentials, Somatosensory / physiology*
  • Fear / physiology*
  • Fear / psychology*
  • Learning / physiology*
  • Male
  • Mice
  • Neuroimaging
  • Ventral Tegmental Area / physiology*


  • Dopamine Plasma Membrane Transport Proteins