While fear plays a fundamental, protective role in our lives, irrational and uncontrollable fear responses are common features of various anxiety disorders that are detrimental to one's quality of daily life. Most contemporary views on fear ascribe preeminent importance to learning, and decades of animal research using the Pavlovian fear conditioning paradigm have made tremendous progress in identifying the neural circuits and mechanisms responsible for the acquisition, maintenance and expression of conditioned fear memories, with a general focus on the amygdala. In contrast to learned fear, innate fear and its effects on risky decisions have largely been overlooked in preclinical and clinical fear research despite its evolutionarily-conserved role in survival. We have recently found that the amygdala regulates both innate fear responses and risky behavior in rats foraging in a seminaturalistic environment with a 'predator-like'robot that is programmed to surge toward the animal as it seeks food. By applying naturalistic 'prey-predator'interactions, the long-term goal of this research is to construct a general experimental and theoretical basis for understanding the functions of fear in ecologically-relevant situations that closely reflect the environments in which fear responses and risky decisions naturally occur. We will incorporate this in a systems-level fear model that can fill the gaps in knowledge, predict new results, and provide insights into the basic approach-avoid conflicts that are thought to underlie human psychopathologies. There are three specific aims of the project: (1) a BEHAVIORAL ANALYSIS will investigate the basic rules of the rat's natural foraging decision in highly quantifiable 'approach food-avoid predator'situations;(2) a SYSTEMS-LEVEL ANALYSIS will reveal the specific roles that the amygdala, medial prefrontal cortex, and hippocampus play in mediating innate fear and risky foraging behavior;and (3) a NEURAL RECORDING ANALYSIS will relate specific components of the animal's behavior to a neural representation of dynamic, affective evaluation in real time. Information generated from this project would be of significance (1) from a basic scientific perspective, providing a more complete picture of fearful behavior in an ecologically-realistic environment;and (2) from an applied perspective, providing insights into developing (and screening the safety of) drug and cognitive- behavioral therapies for generalized anxiety, panic, phobia and posttraumatic stress disorders.

Public Health Relevance

Understanding how fear instinctively guides behaviors and shapes decisions has become increasingly important to the nation's health because of its relevance to clinical conditions and risky behaviors. To fully understand fear, it is vital to investigate its functions in ecologically-relevant situations that closely reflect the environmentsin which fear responses and risky decisions naturally occur. The goal of the proposed project is to directly address the fundamental issue of how fear instinctively influences risky decision making in naturalistic 'approach food-avoid predator'conflict settings and to integrate this into a systems-level model that can fill gaps in the field, predict new results, and inform the treatment of psychopathologies of fear that profoundly impact the quality of human life, such as generalized anxiety, panic, phobia and posttraumatic stress disorders.

National Institute of Health (NIH)
Research Project (R01)
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Neurobiology of Learning and Memory Study Section (LAM)
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Vicentic, Aleksandra
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University of Washington
Schools of Arts and Sciences
United States
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Kim, Earnest; Kim, Eun Joo; Yeh, Regina et al. (2014) Amygdaloid and non-amygdaloid fear both influence avoidance of risky foraging in hungry rats. Proc Biol Sci 281:
Kim, Eun Joo; Horovitz, Omer; Pellman, Blake A et al. (2013) Dorsal periaqueductal gray-amygdala pathway conveys both innate and learned fear responses in rats. Proc Natl Acad Sci U S A 110:14795-800