Active Genetics & Molecular Biology Psychology & Behaviour

The role of genes and life experience in the neural modulation of threat sensitivity

Funder Wellcome Charity-funded
Recipient organisation University College London
Funding £3.2M
Period Sept 2025 — Aug 2032

In plain English

AI plain-English summary

A mouse’s split-second decision to flee or freeze reveals how genes and past experience wire the brain for threat sensitivity. Why this matters: People vary enormously in how they react to danger—some are under-reactive, others over-reactive to harmless situations. This variation underpins anxiety and post-traumatic stress disorders, yet the neural mechanisms that set an individual’s threat sensitivity remain poorly understood. The project focuses on a specific midbrain circuit—the superior colliculus and periaqueductal gray—that transforms sensory cues into escape decisions. By comparing mouse subspecies with naturally different threat sensitivities, and tracking their behaviour and neural activity over weeks, the researchers aim to identify the algorithmic rules that govern this transformation, and how those rules are reshaped by genetic background and life experience. Potential impact: This is fundamental science. It will not produce a treatment tomorrow. But understanding the precise cellular and genetic levers that calibrate threat sensitivity could, in the longer term, point to new targets for therapies that restore appropriate threat processing in anxiety and PTSD—conditions that affect millions and for which current treatments remain inadequate.

View original technical description
The ability to appropriately respond to threats is crucial for survival and requires precise calibration - too little sensitivity leaves individuals vulnerable to danger, while excessive reactions to harmless situations can lead to social isolation and impair quality of life. Individuals show natural variation in threat sensitivity, shaped by both genetic background and lifetime experiences, with disrupted threat processing underlying psychiatric conditions including anxiety and post-traumatic stress disorders. This project investigates how genetic variation and experience shape neural circuits to set threat sensitivity, comparing different mouse subspecies with distinct threat sensitivities while tracking individual behaviour and neural activity over extended periods. Using escape from imminent threats as a model system and focusing on a spatially restricted midbrain circuit, we will identify the algorithmic principles by which the superior colliculus and periaqueductal gray transform sensory stimuli into escape decisions, and how these computations are modified by experience and genetic background. We will determine the cellular and circuit mechanisms implementing these changes and identify key genes regulated through evolution and experience to control threat sensitivity. This research will identify key neural mechanisms regulating threat sensitivity and advance our understanding of individual variations in threat processing. Keywords: threat, escape, midbrain, mouse, experience, genes

View the original record at the funder ↗

Researchers

Tiago Branco (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Neural basis of threat responses
Synaptic integration in the ventromedial hypothalamic nucleus in aggressive behaviour
Computation of innate threats and defensive behaviour in the mouse
The pathophysiology of Autism: developmental trajectories and neuronal networks underlying pathological behaviour in mouse models
Cellular and genetic bases of neural circuits evolution

Original classification

Discovery Award

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.