Basic fear research largely employs the Pavlovian fear conditioning paradigm in rodents. While this model systems approach simplifies behavioral and biological analyses of acquisition, maintenance and expression mechanisms of conditioned fear memories, fear conditioning studies cannot address the fact that animals and humans rely on a multitude of actions and decisions to survive the breadth of risky situations in the real world. Hence, there is a need to complement fear conditioning studies with ecologically-relevant fear research that can lead to novel translational insights. This renewal application will continue to employ and enhance our ?approach food-avoid predator? paradigm to investigate the naturalistic workings of the brain?s fear system. Specifically, in Aim 1, we will examine how rats adapt their fear responses, risk-assessment and foraging decisions to more realistic and diverse risky situations by simulating hidden versus visible threats and terrestrial versus aerial predators. We will also determine the functions of fear conditioning, which has never been analyzed in a naturalistic setting, under realistic prey-predator interaction scenarios.
In Aim 2, we will utilize pharmacology, single unit recordings and optogenetics to further elaborate the neural mechanisms of fear in naturalistic risky conditions. Based on our earlier work, we hypothesize that the dorsal periaqueductal gray-amygdala pathway signals impending threats to elicit innate fear, that the reciprocal medial prefrontal cortex-amygdala circuits serve risk proximity assessment functions, and that the amygdala-hippocampal pathway provides the safety-danger boundary information for adaptive foraging decisions and strategies. This ethologically relevant project is significant (i) from a basic scientific perspective because it will advance a more naturalistic view of the fear system that will fill gaps in knowledge and predict new results, and (ii) from an applied perspective because it can lead to novel insights to develop more effective treatments for generalized anxiety, panic, phobia and posttraumatic stress disorders.
Fear is a primitive and fundamental function of the brain that evolved to protect animals and humans from various ecological threats, such as predation. The proposed experiments in this project will simulate naturalistic predatory threat situations and apply neurobiological techniques in rats to investigate how innate fear, risk- assessment and decision-making function together as the brain's defensive system. Understanding the natural workings of the fear mechanisms and behavior will provide novel insights to developing more effective treatments for psychopathologies of fear, such as generalized anxiety, panic, phobia and posttraumatic stress disorders, which profoundly impact the quality of human life and contribute to the high cost of healthcare in the United States.
Showing the most recent 10 out of 14 publications
