Neuronal Dynamics Regulating Brain and Behavioral State Transitions

Cell. 2019 May 2;177(4):970-985.e20. doi: 10.1016/j.cell.2019.02.037. Epub 2019 Apr 25.


Prolonged behavioral challenges can cause animals to switch from active to passive coping strategies to manage effort-expenditure during stress; such normally adaptive behavioral state transitions can become maladaptive in psychiatric disorders such as depression. The underlying neuronal dynamics and brainwide interactions important for passive coping have remained unclear. Here, we develop a paradigm to study these behavioral state transitions at cellular-resolution across the entire vertebrate brain. Using brainwide imaging in zebrafish, we observed that the transition to passive coping is manifested by progressive activation of neurons in the ventral (lateral) habenula. Activation of these ventral-habenula neurons suppressed downstream neurons in the serotonergic raphe nucleus and caused behavioral passivity, whereas inhibition of these neurons prevented passivity. Data-driven recurrent neural network modeling pointed to altered intra-habenula interactions as a contributory mechanism. These results demonstrate ongoing encoding of experience features in the habenula, which guides recruitment of downstream networks and imposes a passive coping behavioral strategy.

Publication types

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

MeSH terms

  • Adaptation, Psychological / physiology*
  • Animals
  • Behavior, Animal / physiology
  • Brain / metabolism
  • Habenula / metabolism
  • Habenula / physiology*
  • Larva
  • Neural Pathways / metabolism
  • Neurons / metabolism
  • Raphe Nuclei / metabolism
  • Serotonergic Neurons / metabolism
  • Serotonin
  • Stress, Physiological / physiology
  • Zebrafish / metabolism
  • Zebrafish Proteins / metabolism


  • Zebrafish Proteins
  • Serotonin