Researchers Uncover Neural Circuit Mechanism behind Individual Differences in Innate Fear

In a study published in Neuron on May 9, a research team led by Prof. WANG Liping from the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences, has revealed the neural circuit underlying individual differences in visual escape habituation.

Emotional responses, such as fear behaviors, are evolutionarily conserved mechanisms that enable organisms to detect and avoid danger, ensuring survival. Since Darwin's On the Origin of Species (1859) proposed that individual differences drive natural selection, understanding behavioral adaptation has become essential for unraveling biodiversity and survival strategies.

Repeated exposure to predators can elicit divergent coping strategies—habituation or sensitization—that are dependent on sensory inputs, internal physiological states, and prior experiences. However, the neural circuits underlying individual variability in the regulation of internal states and habituation to repeated threats remain poorly understood.

To address this question, Prof. WANG's team employed advanced techniques, such as in vivo multichannel recording, fiber photometry, pupillometry and optogenetic manipulation to investigate how individual differences in arousal and internal states influence visual escape habituation.

The key finding of the study is that distinct subcortical pathways from the superior colliculus to the amygdala and insula cortical pathways that govern two visual escape behaviors in two groups of mice. 

This study systematically identified two distinct defensive behaviors-sustained rapid escape (T1) and rapid habituation (T2). T1 involves superior colliculus (SC)/insular cortex-ventral tegmental area (VTA)-basolateral amygdala (BLA) pathway, whereas T2 relies on SC/insula -dorsomedial thalamus (MD)-BLA circuit. The MD integrates inputs from the SC and insula to regulate arousal and fear responses, while beta oscillations in BLA modulate fear states.

"Dysregulation of innate fear circuits is closely linked to many mental health conditions, including phobias, anxiety, and post-traumatic stress disorder (PTSD). Therefore, elucidating the neural circuitry underlying innate fear not only enhances our understanding of emotional disorders but also provides promising therapeutic targets for clinical interventions." said Prof. WANG.

"Our work provides new insights into arousal modulation, internal states, and adaptive responses to visual threats." said Prof. LIU Xuemei, first author and co-corresponding author of the study.

By elucidating the neural basis of individual differences in fear plasticity, this study highlights the central role of brain states in stress adaptation, offering new perspectives and potential therapeutic targets for anxiety, depression, and PTSD. 

Arousal-state-dependent neural circuits drive variability in innate fear responses. (Image by SIAT)