Composition of prefrontal ensembles in virtual fear of heights decision-making task

An animal’s ability to evaluate environmental threats and mount an appropriate behavioral response is critical to survival. Based on previous literature in rodents and humans, we developed a novel rodent fear of heights task which is highly controllable and can be used to interrogate neural computations underlying innate threat processing. We developed a virtual height threat task in which animals are placed on a pole and must choose to exit to either a “close” or “far” virtual platform. We find that animals perform around chance levels when the discrepancy between visual stimuli is small (5cm) but choose the “close” platform significantly more often when the discrepancy is large (20cm). Fiber photometry of calcium in the locus coeruleus (LC) and norepinephrine (NE) in the medial prefrontal cortex (mPFC) reveals these regions respond to height threat and the threat signal dissipates once the animal transitions from height exposure to safety. Single cell calcium imaging of mPFC neurons demonstrates a similar activation pattern on a population level, but that individual neurons display distinct response patterns to height threat exposure and at the decision point. As norepinephrine is known to play a role in both arousal and fear, leveraging a highly controllable visual threat behavior will allow for dissection of the neural computations underlying norepinephrine’s role in exploratory versus defensive behaviors. How individual neurons work within ensembles to differentially encode height threat and influence decision making given the same NE input poses an interesting question for understanding communication within and between neural networks.