Can we change the way our brain responds to fear? While fear can be essential for survival, it can also become excessive, resulting in disorders such as anxiety and phobias that impair daily life. Recent research from the Sainsbury Wellcome Centre at UCL questions what we know about the brain regions associated with fear, suggesting future interventions to overcoming fear. By Rebecca Manzini
What if the key to overcoming fear is not just facing it, but rewiring your brain to no longer respond to it? Fear is essential for survival. It alerts us to potential dangers and triggers instinctive responses that keep us safe. However, when this becomes excessive or misdirected, fear can manifest as anxiety disorders, phobias, or post-traumatic stress disorder (PTSD), impairing daily life. The ability to suppress fear responses when a threat is no longer present is a key aspect of adaptive behaviour. Recent neuroscience research conducted at the Sainsbury Wellcome Centre at University College London has revealed a previously unrecognized brain mechanism which helps override instinctive fear responses, offering new insights into fear regulation and potential treatments for anxiety-related conditions.
For decades, scientists have understood that fear is processed in the brain’s amygdala and brainstem circuits, which trigger rapid, instinctive responses to threats (Cleveland Clinic, 2023). The posterior lateral hypothalamic area (plHVA) was revealed to be essential for the learning phase of suppressing fear responses to stimuli, nonetheless, the study investigates how this is not necessary once this learned behaviour has been established (Mederos et al., 2025). The ventral lateral geniculate nucleus (vLGN), a lesser-known brain region that appears to store learned safety memories and suppress instinctive fear responses over time, seems to play a role in this (Ktori, 2025).
In the study, researchers stimulated a predatory threat on mice using an overhead expanding shadow. Initially, the mice fled in fear, but after repeated exposure without actual danger, they learned to remain calm. By tracking neural activity using silicon probes, the scientists observed that the visual cortex was no longer required, and the fear suppression was solely controlled by the vLGN (Sands, 2025). The researchers then performed optogenetic mutations, meaning they switched specific types of neurons on or off using light. They found that plHVA, working in the visual cortex, is crucial for learning to suppress instinctive fear, but unnecessary for maintaining the behaviour once learned. Instead, this relies on plasticity within the vLGN that exerts inhibitory control over escape responses. When the vLGN was silenced in the mice trained to suppress fear, they became scared of the threatening shadows once again. By tracking neural responses to stimuli before, during, and after the learning phase, researchers observed that many vLGN neurons exhibited increased firing rates to stimuli after learning (Mederos et al., 2025). Notably, this increase in neural activity was correlated with the behavioural suppression of escape responses. This was an unusual result as this area of the brain is not normally thought to be capable of plasticity, as stated by co-author Sara Mederos, a system neuroscientist at UCL (Mederos et al., 2025).
Furthermore, the study also showed that inhibiting chemicals in the body known as endocannabinoids (brain-internal messenger molecules known to regulate mood and memory) prevented mice from learning how to suppress their fears (Ktori, 2025). Learning occurs through increased neural activity by specific vLGN neurons, and this is triggered by the release of endocannabinoids (eCBs). Specifically, long-term depression (LTD) of inhibitory synapses in vLGN neurons was found to mediate the learning process. This form of plasticity, known as inhibitory long-term depression (iLTD), is dependent on eCB signaling, which reduces the inhibitory input onto vLGN neurons activated by plHVAs. The reduction of inhibitory input allows vLGN neurons to become more excitable, therefore promoting the learned suppression of escape responses (Mederos et al., 2025). When endocannabinoid activity was inhibited, the mice failed to learn fear suppression, suggesting that these neurotransmitters are vital for modulating anxiety and fear regulation.
Overall, the experiments conducted by the team contradict the traditional view that the cerebral cortex is the primary centre for learning and memory, highlighting instead the vLGN as a key storage site for learned fear suppression, demonstrating that the brainstem is more adaptable than previously believed. This provides a potential explanation for why individuals with PTSD or anxiety disorders struggle to suppress irrational fears: their vLGN circuits may not be functioning properly (Ktori, 2025). This could provide a new understanding for possible treatments such as deep brain stimulation or pharmacological interventions that enhance endocannabinoid activity to reinforce fear suppression. Traditional treatments for anxiety disorders, such as cognitive behavioral therapy (CBT), focus on reframing fear-inducing thoughts, however, these findings suggest that directly targeting the vLGN or modulating endocannabinoid activity could reinforce safety learning more effectively.
The discovery of the vLGN’s role in fear suppression marks a significant shift in neuroscience, where the hope is that these insights will translate into practical interventions, helping individuals harness their brain’s natural ability to overcome fear.
References
Cover Image: https://www.pexels.com/search/fear/
Mederos, S., Blakely, P., Vissers, N., Clopath, C. and Hofer, S.B. (2025). Overwriting an instinct: Visual cortex instructs learning to suppress fear responses. Science, 387(6734), pp.682–688. doi:https://doi.org/10.1126/science.adr2247.
Sands, L. (2025). Scientists say they’ve discovered how the brain overcomes fear. [online] Washington Post. Available at: https://www.washingtonpost.com/science/2025/02/06/fear-human-brain-mouse-study/.
Ktori, S. (2025). Brain Mechanism for Overcoming Instinctive Fears Identified in Mice. [online] GEN - Genetic Engineering and Biotechnology News. Available at: https://www.genengnews.com/topics/translational-medicine/brain-mechanism-for-overcoming-instinctive-fears-identified-in-mice/.
Cleveland Clinic (2023). Amygdala. [online] Cleveland Clinic. Available at: https://my.clevelandclinic.org/health/body/24894-amygdala.
