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Defensive responses: behaviour, the brain and the body

Nature Reviews Neuroscience volume 24, pages 655–671 (2023)Cite this article

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Abstract

Most animals live under constant threat from predators, and predation has been a major selective force in shaping animal behaviour. Nevertheless, defence responses against predatory threats need to be balanced against other adaptive behaviours such as foraging, mating and recovering from infection. This behavioural balance in ethologically relevant contexts requires adequate integration of internal and external signals in a complex interplay between the brain and the body. Despite this complexity, research has often considered defensive behaviour as entirely mediated by the brain processing threat-related information obtained via perception of the external environment. However, accumulating evidence suggests that the endocrine, immune, gastrointestinal and reproductive systems have important roles in modulating behavioural responses to threat. In this Review, we focus on how predatory threat defence responses are shaped by threat imminence and review the circuitry between subcortical brain regions involved in mediating defensive behaviours. Then, we discuss the intersection of peripheral systems involved in internal states related to infection, hunger and mating with the neurocircuits that underlie defence responses against predatory threat. Through this process, we aim to elucidate the interconnections between the brain and body as an integrated network that facilitates appropriate defensive responses to threat and to discuss the implications for future behavioural research.

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Fig. 1: Defensive responses across the three phases of the threat imminence continuum and the underlying brain circuits.
Fig. 2: Transmission routes of infection signals to the brain.
Fig. 3: Crosstalk between the digestive system and the brain.
Fig. 4: Brain–body interactions modulating defensive behaviours.

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Acknowledgements

The authors thank all scientists whose studies were reviewed in this paper and apologize to those whose work was not cited owing to space limitations. The authors thank B. H. Zhao for assistance with illustrations. This work was supported by grants from the National Natural Science Foundation of China (32230042 and 31930047 to L.W., 32200826 to Y.-T.T. and 32222036 to P.W.), the Shenzhen Science and Technology Program (KCXFZ20211020163549011 to B.S. and JCYJ20220530154412028 to Y.-T.T.) and the Financial Support for Outstanding Talents Training Fund in Shenzhen (L.W.).

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  1. CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China

    Yu-Ting Tseng, Bernhard Schaefke, Pengfei Wei & Liping Wang

  2. Guangdong Provincial Key Laboratory of Brain Connectome and Behaviour, the Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China

    Yu-Ting Tseng & Liping Wang

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Glossary

Adaptive behaviour

Behaviour is adaptive in an evolutionary sense if it increases genetic fitness, usually by promoting the survival and reproduction of an organism or that of close kin, which can coincide with negative emotional states such as anxiety or fear.

Auditory looming assay

Behavioural test in which an animal is exposed to sudden increasing sounds induced by broadband white noise, triggering circa-strike phase defensive behaviours.

Conditioned fear

A learned defensive response elicited by a previously neutral stimulus (conditioned stimulus) that has been paired with an aversive event (unconditioned stimulus).

Defence vigour

Physical strength of the execution of defensive behaviours. For example, an increase in speed during escape and increased durations of avoidance or persistent freezing can be considered increased defence vigour.

Dysbiotic microbiota

An imbalance or disruption in bacterial composition, metabolic activities or distribution within the intestinal tract, often leading to negative health consequences such as inflammation and disease.

Elevated plus maze

Behavioural test in which an animal explores elevated open and enclosed arms and in which reduced entries into open arms indicate enhanced defensive behaviour in the pre-encounter phase and an anxiety-like state.

Maladaptive behaviour

Behaviour patterns that are adaptive in some contexts can become maladaptive in an evolutionary sense when they are displayed in the wrong context or with excessive vigour and, thereby, prevent the execution of adequate adaptive behaviours, ultimately reducing the survival chances and reproductive success of the organism.

Open field test

Behavioural test in which an animal explores an unstructured open arena and the increased avoidance of central areas indicates enhanced defensive behaviours in the pre-encounter phase (often referred to as anxiety-related behaviour).

Optogenetics

An approach involving the expression of light-sensitive ion channels or pumps in specific cells, allowing cellular or organ activity to be manipulated by light with high spatial and temporal precision.

Phase shifts in the threat imminence continuum

Phase shifts in the threat imminence continuum refer to the phenomenon when behaviour patterns typical for one phase of the continuum are activated earlier (at lower imminence) or later (at higher imminence) than typically observed. They may be adaptive in some contexts or maladaptive in others.

Visual looming assay

Behavioural test in which an animal is exposed to rapidly expanding dark overhead spots that serve as visual cues simulating approaching threats, triggering circa-strike phase defensive behaviours.

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Tseng, YT., Schaefke, B., Wei, P. et al. Defensive responses: behaviour, the brain and the body. Nat. Rev. Neurosci. 24, 655–671 (2023). https://doi.org/10.1038/s41583-023-00736-3

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