Neuronal Dynamics Regulating Brain and Behavioral State Transitions

Aaron S. Andalman, Vanessa M. Burns, Matthew Lovett-Barron, Michael Broxton, Ben Poole, Samuel J. Yang, Logan Grosenick, Talia N. Lerner, Ritchie Chen, Tyler Benster, Philippe Mourrain, Marc Levoy, Kanaka Rajan, Karl Deisseroth

Research output: Contribution to journalArticlepeer-review

95 Scopus citations


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. Brainwide imaging in zebrafish and network modeling reveal that switching from active to passive coping state arises from progressive activation of habenular neurons in response to behavioral challenge.

Original languageEnglish
Pages (from-to)970-985.e20
Issue number4
StatePublished - 2 May 2019


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