Frontal cortex norepinephrine, serotonin, and dopamine dynamics in an innate fear-reward behavioral model

Abstract

AbstractAnimals must survive by foraging for food in an uncertain and dangerous world. Experimental tasks such as Pavlovian learning have yielded insights into how neural circuits balance these conflicting motivational drives. Neuromodulators play a fundamental role in this process, enabling flexible switching between motivational drives. The question of how neuromodulators synergistically encode motivational state is thus fundamental to systems neuroscience, yet the interplay between these neuromodulators during naturalistic decision making are not fully understood. Here, we developed a naturalistic approach/avoidance task in mice involving a tradeoff between seeking reward versus safety in the presence of looming predation risk. We utilized multi-fiber photometry, computational behavior tracking, and slice electrophysiology to understand the. Mice that experienced looming stimuli showed increased c-fos expression in regions including frontal cortex, locus coeruleus, and ventral tegmental area, but decreased expression in dorsal raphe nucleus. Moreover, by using multi-fiber photometry combined with GPCR-based sensors, we found that cortical norepinephrine (NE) plays a more prominent role in encoding looming threats while dopamine (DA) represents reward and threat. In contrast, serotonin (5HT) dynamic negatively correlates to both emotional valences. To begin to understand neuromodulatory interactions, we usedex vivoslice physiology to understand 5HT impact on spontaneous firing of locus coeruleus NE neurons. In conclusion, monoamines such as NE, DA, 5HT can converge in their encoding of naturalistic motivated behaviors as well as dissociate from one another. By utilizing this approach, interactions between innate fear and incentive for food may be delineated in terms of basis in neurochemical signaling events during natural behavior, and may contribute to the understanding of neural mechanisms underlying emotional disorders including anxiety and post-traumatic stress disorder.