Dopaminergic circuits controlling threat and safety learning

Trends Neurosci. 2024 Dec;47(12):1014-1027. doi: 10.1016/j.tins.2024.10.001. Epub 2024 Oct 28.

Abstract

The ability to learn from experience that certain cues and situations are associated with threats or safety is crucial for survival and adaptive behavior. Understanding the neural substrates of threat and safety learning has high clinical significance because deficits in these forms of learning characterize anxiety disorders. Traditionally, dopamine neurons were thought to uniformly support reward learning by signaling reward prediction errors. However, the dopamine system is functionally more diverse than was initially appreciated and is also critical for processing threat and safety. In this review, I highlight recent studies demonstrating that dopamine neurons generate prediction errors for threat and safety, and describe how dopamine projections to the amygdala, medial prefrontal cortex (mPFC), and striatum regulate associative threat and safety learning.

Keywords: amygdala; fear conditioning; fear extinction; medial prefrontal cortex; reward; striatum.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / physiology
  • Animals
  • Dopamine / metabolism
  • Dopaminergic Neurons* / physiology
  • Fear / physiology
  • Humans
  • Learning* / physiology
  • Neural Pathways / physiology
  • Prefrontal Cortex / physiology
  • Safety

Substances

  • Dopamine