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

Neuronal Dynamics Regulating Brain and Behavioral State Transitions.

Author information

1
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; CNC Program, Stanford University, Stanford, CA 94305, USA.
2
Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.
3
Department of Computer Science, Stanford University, Stanford, CA 94305, USA.
4
Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA.
5
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Neurosciences Program, Stanford University, Stanford, CA 94305, USA.
6
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
7
Neurosciences Program, Stanford University, Stanford, CA 94305, USA.
8
Stanford Center for Sleep Sciences and Medicine, Stanford University, Stanford, CA 94305, USA; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; INSERM U1024, Ecole Normale Supérieure Paris, Paris 75005, France.
9
Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
10
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; CNC Program, Stanford University, Stanford, CA 94305, USA; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA. Electronic address: deissero@stanford.edu.

Abstract

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.

PMID:
31031000
DOI:
10.1016/j.cell.2019.02.037

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