Mice Override Instinctive Fear Responses Uncovered

Researchers have uncovered a neural mechanism in the brains of mice that enables them to override instinctive fear responses; dysfunction in this mechanism may contribute to inappropriate or excessive fear responses, they say. According to the findings, targeting these circuits could offer new therapeutic avenues for treating fear-related disorders like post-traumatic stress disorder and anxiety. Fear responses to visual threats, such as escaping from an approaching predator, are critical instinctive reactions for survival and are primarily managed by brainstem circuits involving the medial superior colliculus and periaqueductal gray. These reflexive actions are typically automatic and independent of higher brain regions. However, animals can suppress these fear responses upon learning that a perceived threat is harmless. However, the neural mechanisms and brain regions behind this form of learning, which modifies instinctive reactions, remain poorly understood. Escape behavior in response to a looming visual stimulus is a well-established measure of instinctive fear, where naïve mice typically flee to a shelter when presented with such a threat. Hara Mederos and colleagues designed an experiment in which mice were prevented from accessing shelter by a visual stimulation threat rendered from a projector – three consecutive expanding black spots in a 3-second period. Over time, the mice learned to stop escaping from the black spots. Using optogenetic techniques during various stages of this learning process, Mederos et al. found that posterolateral higher visual areas (plHVA) – a group of brain regions in the visual cortex – are crucial for learning to suppress instinctive fear responses. However, the visual cortex is not necessary for maintaining the behavior once learned. Instead, plasticity occurs downstream in the ventrolateral geniculate nucleus (vLGN), where neurons receive inhibitory modulation driven by experience. This plasticity, dependent on endocannabinoid (eCB) signaling, decreases inhibitory input to vLGN neurons, facilitating suppression of escape behaviors. According to the authors, targeting these pathways, such as through deep brain stimulation or enhancing eCB-dependent plasticity within these circuits, could help suppress maladaptive fear responses, offering potential new therapeutic approaches.