Our brains integrate sensory information with prior knowledge to guide our decisions and generate behavioural outcomes. However, through which neural pathways prior experience can adapt behavioural responses to sensory input is still unclear.

 Vision involves various behavioral functions such as visual navigation, predator avoidance, and stimulus–reward learning. As the higher visual areas (HVAs) reside at higher tiers of the visual processing hierarchy and exhibit strong connections with associational and nonvisual areas, a potential role of HVAs is to integrate behavioral and cognitive signals, to facilite adaptive behavior in accordance with task demands (Glickfeld LL & Olsen SR. Higher-Order Areas of the Mouse Visual Cortex. Annu Rev Vis Sci. 2017).

 Predator-avoidance behaviors, particularly escape from visual threat, are essential due to their evolutionary significance. However, after frequently being exposed to threat stimulus mice habituate – they stop escaping once they have learned that the stimulus does not pose a real danger (Lenzi SC et al. Threat history controls flexible escape behavior in mice. Curr Biol. 2022). Here we focused on such a simple learned suppression of innate fear to answer if the representation of prior experience may be a general feature of HVAs facilitating learning to suppress escape.

 We found that silencing lateral HVAs projections to the ventral lateral geniculate nucleus (vLGN), an inhibitory nucleus in the prethalamus, during the learning protocol prevented the suppression of fear, as mice kept escaping to a threating stimulus. Silencing HVAs after habituation had no effect on escape responses. These findings suggest that input from higher visual cortices, specifically during habituation, induces learning in vLGN circuits. We used electrophysiological single-unit recordings with chronically implanted probes in vLGN. We performed spectral clustering on the population of vLGN neurons and identified a subset of vLGN neurons that exhibited increased activity after mice had learned. Furthermore, we discovered that these cells specifically receive direct input from the HVAs.

 Our study has confirmed the involvement of specific inhibitory cells in vLGN during experience-driven suppression of fear responses. Additionally, we have established the role of the HVAs in instructing these changes, unveiling the circuit mechanisms underlying mice’s ability to overcome innate fear.

More information:

• https://www.sainsburywellcome.org/web/people/sara-mederos