Paralyzing fear: researchers characterise neural circuits that underlie passive coping

IMP scientists have characterised a mechanism that reprograms specific neural circuits so that mice respond to stress with passive behaviour. The mechanism could also contribute to passive emotional coping as seen in people with fear- and anxiety disorders.

Learning from experience is key to survival, as it allows animals to optimise how they respond to recurring situations. Animals often react to stress by switching from active to passive behaviours to avoid potential danger and increase their chance of survival. This effect that can also be observed in humans – who, when stressed, may retract from socially or emotionally challenging situations. However, the neural basis for this stress induced shift in behavioural responding remained unclear.

Scientists from the lab of Wulf Haubensak at the Research Institute of Molecular Pathology (IMP) in Vienna now report a detailed mechanism which controls this in the journal ‘Molecular Psychiatry’.

“We investigated stress effects by placing mice in an ‘elevated plus maze’, a behavioural arena. Animals typically can respond to this challenge either with active exploration or passive freezing.”, says Pinelopi Pliota, first author of the paper. “When the animals were previously stressed, they switched their behaviour from actively running around to passive freezing.”

“What we found is that essentially, stress can release certain peptides which reprogram the amygdala and sensitizes groups of neurons associated with passive freezing”, says Wulf Haubensak. “As a result, after stress, the animals respond to the same behavioural challenge by switching to more passive responses.” What Haubensak summarises in these simple words is the outcome of sophisticated experiments including deep brain calcium imaging and optogenetic manipulations of neurons in freely moving mice. “Interestingly, the activity of the amygdala neurons and passive behaviour was reduced when we administered a drug that blocks the receptor of the peptide.”

The study shows how behavioural plasticity can be controlled on the level of individual circuits of neurons. Moreover, it establishes a framework for stress-induced passive responding, which the authors hope will explain passive emotional coping in people with emotional conditions such as fear- or anxiety-related disorders.

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Original Publication
Pliota, P. et al., (2018). „Stress peptides sensitize fear circuitry to promote passive coping”. Molecular Psychiatry. DOI: https://doi.org/10.1038/s41380-018-0089-2

Videos
Occupancy plots of a mouse: video EPM A shows the mouse actively exploring the arena, as opposing to video EPM B, where it occupies only the closed arm of the arena and shows passive behaviour.