Although significant advances have been made in elucidating the structures that regulate fear and food- seeking responses in isolation, the neural circuits and mechanisms that integrate both behavioral responses remain poorly understood. Previous studies have shown that the paraventricular nucleus of the thalamus (PVT) is interconnected with areas of the brain implicated in the control of fear and food-seeking responses. We have recently shown that neurons in the anterior part of PVT (aPVT) respond differently to aversive and rewarding stimuli, suggesting that this region may be part of a core neural network that integrates fear and food-seeking responses. Using an experimental approach in which rats need to overcome their fear of predator cues in order to search for food, in Aim 1 we will identify potential inputs that convey predator threat and food reward information to aPVT neurons by using a combination of neural tracers, immunohistochemistry, and electrophysiological recordings in vitro.
In Aim 2, we will use optogenetics and single-unit recordings to manipulate and record from aPVT-projecting neurons during the predator threat vs. food-seeking conflict test. We will then correlate neural activity with distinct behavioral responses.
In Aim 3, we will record from specific subsets of aPVT neurons while chemogenetically manipulating input regions that transmit threat- and food- related information to aPVT neurons. The experiments proposed in these three aims will provide insights into elucidating the competing demands of avoiding threats and approaching rewards, which may have clinical relevance for understanding adaptive and motivated behaviors.
This project will investigate the neural circuits and mechanisms responsible for integrating the opposing drives of avoiding threats and seeking for rewards. Whereas exaggerated reward seeking is a hallmark of substance abuse and eating disorders, persistent avoidance is the most debilitating symptom of many fear-related disorders. Our ethologically-relevant paradigm combining natural threats with food cues will lead to a better understanding of how the brain computes threatening and rewarding information to generate distinct patterns of behavior.
