Developing a Behavioral Model for Studying Visual Evoked Conditioned Threat Reactivity in Mice

Background: Visual threat processing is essential for survival, allowing organisms to rapidly respond to potential danger. Emerging evidence indicates that the ventral lateral geniculate nucleus (vLGN) of the thalamus plays a key role in processing visual threats to prior experience. Building on this, we used a Pavlovian fear conditioning paradigm, combined with an overhead looming disk (threat) stimulus to test if mice could be conditioned to respond defensively to visual threats in a new environmental context (ie., home cage). We hypothesized that the pairing of the looming disk (unconditioned stimulus) with an auditory tone (conditioned stimulus), will elicit a CS-evoked visual threat defensive response in a new context. Methods: Two groups of mice were tested (n = 7 per group): a control group exposed solely to the looming disk (LD) and an experimental group exposed to both the looming disk and a high-pitched tone (LDT). The tone used was 70-dB, and the disc simulated an aerial predator with expansion to 20 degrees in 0.5 seconds. The experiment involved a four-day protocol consisting of habituation, transfer, and conditioning phases, followed by testing in the home cage. During testing, six tones were played at random intervals over a 24 hour period, and freezing behavior was recorded during the 30 seconds before each tone ("Pre") and the 30 seconds after each tone ("Post"). Results: Data showed that the LDT group exhibited a conditioned CS-evoked freezing response in the home cage, with significantly increased freezing compared to the LD group during "Pre" (37.35% vs. 28.97%, p = 0.01) and "Post" (51.97% vs. 31.65%, p = 0.004) periods in daytime trials. Compared to LD alone, the LDT group's freezing progressively increased from "Pre" to "Post," indicating effective conditioning. Conversely, during nighttime trials, the LD group displayed higher freezing patterns compared to the LDT group during "Pre" (33.62% vs. 28.01%, p = 0.03) and "Post" (70.1% vs. 60.1%, p = 0.04), suggesting diurnal differences in fear responses. Conclusion: These findings demonstrate a proof-of-principle novel behavioral model for studying conditioned visual threat processing and the role of a conditioned prior experience. This model may have implications for further understanding visual threat circuits, such as the vLGN and role in visual threat behavioral responses, and may have implications for PTSD. This research was supported by the Psychological and Brain Sciences Undergraduate Research and Service Grant. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.