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Neuronal Dynamics Regulating Brain and Behavioral State Transitions.

Aaron S Andalman1, Vanessa M Burns2, Matthew Lovett-Barron1

  • 1Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; CNC Program, Stanford University, Stanford, CA 94305, USA.

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|April 30, 2019
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Summary
This summary is machine-generated.

Animals switch to passive coping under stress, which can be maladaptive in depression. This study reveals ventral habenula neuron activation drives this passive coping strategy by suppressing downstream brain networks.

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Area of Science:

  • Neuroscience
  • Behavioral Biology
  • Psychiatry

Background:

  • Prolonged stress can shift coping strategies from active to passive, a transition that may become maladaptive in conditions like depression.
  • The neural mechanisms and brain-wide interactions governing passive coping remain poorly understood.
  • Understanding these mechanisms is crucial for addressing psychiatric disorders characterized by altered coping behaviors.

Purpose of the Study:

  • To investigate the cellular-resolution neuronal dynamics underlying behavioral state transitions to passive coping.
  • To elucidate the brain-wide interactions involved in the shift from active to passive stress coping.
  • To identify specific brain regions and neuronal populations critical for passive coping strategies.

Main Methods:

  • Development of a novel paradigm for studying behavioral state transitions at cellular resolution across the vertebrate brain.
  • Utilizing whole-brain imaging in zebrafish to observe neuronal activity during stress-induced coping shifts.
  • Employing recurrent neural network modeling to analyze habenula circuit dynamics.

Main Results:

  • The transition to passive coping was correlated with progressive activation of ventral (lateral) habenula neurons.
  • Activation of ventral habenula neurons led to suppression of downstream serotonergic raphe nucleus neurons, inducing behavioral passivity.
  • Inhibition of these specific habenula neurons prevented the onset of passive coping behavior.
  • Neural network modeling suggested altered intra-habenula interactions contribute to passive coping.

Conclusions:

  • The ventral habenula plays a critical role in imposing passive coping strategies by modulating downstream neural networks.
  • Neuronal activity within the habenula encodes experience features that guide the recruitment of specific behavioral outputs.
  • These findings offer insights into the neural basis of maladaptive passive coping in psychiatric disorders like depression.