Expanding the canon: An inclusive neurobiology of thalamic and subthalamic fear circuits

Neuropharmacology. 2023 Mar 15:226:109380. doi: 10.1016/j.neuropharm.2022.109380. Epub 2022 Dec 23.


Appropriate expression of fear in the face of threats in the environment is essential for survival. The sustained expression of fear in the absence of threat signals is a central pathological feature of trauma- and anxiety-related disorders. Our understanding of the neural circuitry that controls fear inhibition coalesces around the amygdala, hippocampus, and prefrontal cortex. By discussing thalamic and sub-thalamic influences on fear-related learning and expression in this review, we suggest a more inclusive neurobiological framework that expands our canonical view of fear. First, we visit how fear-related learning and expression is influenced by the aforementioned canonical brain regions. Next, we review emerging data that shed light on new roles for thalamic and subthalamic nuclei in fear-related learning and expression. Then, we highlight how these neuroanatomical hubs can modulate fear via integration of sensory and salient stimuli, gating information flow and calibrating behavioral responses, as well as maintaining and updating memory representations. Finally, we propose that the presence of this thalamic and sub-thalamic neuroanatomy in parallel with the tripartite prefrontal cortex-amygdala-hippocampus circuit allows for dynamic modulation of information based on interoceptive and exteroceptive signals. This article is part of the Special Issue on "Fear, Anxiety and PTSD".

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Anxiety Disorders
  • Brain* / physiology
  • Fear* / physiology
  • Humans
  • Learning / physiology
  • Thalamus