Circuits regulating arousal and behavioral responses to visual threats - PROJECT SUMMARY The ability to appropriately respond to threats is crucial for survival. Literature has long suggested that arousal and attention, mediated by the neuromodulators norepinephrine (NE) and acetylcholine (ACh), influence sensory processing. NE and ACh release affect behavioral states and are released in response to novelty, attentional effort, and threat. However, the unique contributions of these neuromodulators in regulating behavioral states, and circuits which might underly the release of these neuromodulators in response to salient threat stimuli, remain unclear. It is possible that salient visual stimuli alter neuromodulator release through direct projections of the superior colliculus, resulting in enhanced sensory processing in response to threat, but this circuit has not been directly tested. Height threat is an evolutionarily conserved, ethological visual threat behavior that can be used to study neural circuits underlying threat processing. The visual cliff test is an optical illusion which generates the appearance of a cliff. Both rodents and human infants avoid crossing the threshold of the visual cliff. In rodents, this behavior depends on visual perception and binocular vision. Humans exposed to virtual height threats exhibit increased physiological arousal which correlates with perceived height level. We developed a virtual visual cliff task to study the relationship between neuromodulators, attention, arousal, sensory processing, and threat-related decision-making. Mice climb down a pole towards a virtual cliff and exit to one of four quadrants, one which appears close and three which appear distant. Threat level is modulated by altering the apparent distance between the close and distant quadrants. Head-mounted eye tracking will be used to measure arousal via pupil diameter and attention via gaze and head direction, which will allow us to differentiate the roles of attention and arousal in visual processing and decision-making. This research will elucidate how neuromodulators influence sensory encoding and behavior in response to visual threats, as well as the role of sensory systems in engaging neuromodulator release to enhance sensory processing in response to salient visual threats.
