A hypothalamic-thalamostriatal circuit that controls approach-avoidance conflict in rats

Nat Commun. 2021 May 4;12(1):2517. doi: 10.1038/s41467-021-22730-y.


Survival depends on a balance between seeking rewards and avoiding potential threats, but the neural circuits that regulate this motivational conflict remain largely unknown. Using an approach-food vs. avoid-predator threat conflict test in rats, we identified a subpopulation of neurons in the anterior portion of the paraventricular thalamic nucleus (aPVT) which express corticotrophin-releasing factor (CRF) and are preferentially recruited during conflict. Inactivation of aPVTCRF neurons during conflict biases animal's response toward food, whereas activation of these cells recapitulates the food-seeking suppression observed during conflict. aPVTCRF neurons project densely to the nucleus accumbens (NAc), and activity in this pathway reduces food seeking and increases avoidance. In addition, we identified the ventromedial hypothalamus (VMH) as a critical input to aPVTCRF neurons, and demonstrated that VMH-aPVT neurons mediate defensive behaviors exclusively during conflict. Together, our findings describe a hypothalamic-thalamostriatal circuit that suppresses reward-seeking behavior under the competing demands of avoiding threats.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avoidance Learning / physiology*
  • Behavior Rating Scale
  • Conflict, Psychological
  • Corticotropin-Releasing Hormone / metabolism*
  • Female
  • Hypothalamus / metabolism
  • Hypothalamus / physiology*
  • Male
  • Midline Thalamic Nuclei / cytology
  • Midline Thalamic Nuclei / drug effects
  • Midline Thalamic Nuclei / metabolism*
  • Midline Thalamic Nuclei / radiation effects
  • Nerve Net / physiology*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Nucleus Accumbens / metabolism
  • Nucleus Accumbens / physiology
  • Nucleus Accumbens / radiation effects
  • Optogenetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Reward
  • Ventromedial Hypothalamic Nucleus / cytology
  • Ventromedial Hypothalamic Nucleus / physiology*


  • Proto-Oncogene Proteins c-fos
  • Corticotropin-Releasing Hormone