Transfer to a naturalistic setting restructures fear responses in laboratory mice

Appropriate classification of a novel stimulus as threatening or benign depends on a repertoire of prior environmental experiences involving challenge, risk, and opportunity¹

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Asok, A. ∙ Kandel, E.R. ∙ Rayman, J.B.

The neurobiology of fear generalization

Front. Behav. Neurosci. 2019; 12:329

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^,2

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Dunsmoor, J.E. ∙ Paz, R.

Fear generalization and anxiety: Behavioral and neural mechanisms

Biol. Psychiatry. 2015; 78:336-343

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. Without this library, individuals may classify harmless stimuli as dangerous — a hallmark of generalized anxiety¹

1.

Asok, A. ∙ Kandel, E.R. ∙ Rayman, J.B.

The neurobiology of fear generalization

Front. Behav. Neurosci. 2019; 12:329

Google Scholar

^,2

2.

Dunsmoor, J.E. ∙ Paz, R.

Fear generalization and anxiety: Behavioral and neural mechanisms

Biol. Psychiatry. 2015; 78:336-343

Google Scholar

. In humans, insufficient exposure to uncertainty or manageable risks is associated with heightened anxiety and maladaptive fear generalization and is theorized to contribute to rising rates of anxiety in children³

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Dodd, H.F. ∙ Lester, K.J.

Adventurous play as a mechanism for reducing risk for childhood anxiety: A conceptual model

Clin. Child Fam. Psychol. Rev. 2021; 24:164-181

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4.

Favril, L. ∙ Rich, J.D. ∙ Hard, J. ...

Mental and physical health morbidity among people in prisons: An umbrella review

Lancet Public Health. 2024; 9:e250-e260

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^,5

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King, L.S. ∙ Guyon-Harris, K.L. ∙ Valadez, E.A. ...

A comprehensive multilevel analysis of the bucharest early intervention project: Causal effects on recovery from early severe deprivation

Am. J. Psychiatry. 2023; 180:573-583

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. Although animals in natural environments accumulate a wide range of experiences that allow them to calibrate threat assessment, most behavioral studies of anxiety rely on laboratory animals housed in static, impoverished conditions. In this laboratory context, the widely used elevated plus maze (a measure of anxiety) induces a persistent fear response in mice after a single exposure. Here we show that transferring adult mice from the lab to a large field enclosure mimicking natural mouse environments was sufficient to block the development of this fear response and restore baseline levels of anxiety behavior. A canonical rodent anxiety phenotype is thus environmentally contingent and rapidly reversible, underscoring the risks of inferring general behavioral principles from impoverished housing conditions.