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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH099073-02
Application #
8699271
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Vicentic, Aleksandra
Project Start
2013-07-15
Project End
2018-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Washington
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
City
Seattle
State
WA
Country
United States
Zip Code
98195
Kim, Eun Joo; Kong, Mi-Seon; Park, Sang Geon et al. (2018) Dynamic coding of predatory information between the prelimbic cortex and lateral amygdala in foraging rats. Sci Adv 4:eaar7328
Huh, Yeowool; Jung, Dahee; Seo, Taeyoon et al. (2018) Brain stimulation patterns emulating endogenous thalamocortical input to parvalbumin-expressing interneurons reduce nociception in mice. Brain Stimul 11:1151-1160
Kim, Jeansok J; Jung, Min Whan (2018) Fear paradigms: The times they are a-changin'. Curr Opin Behav Sci 24:38-43
Pellman, Blake A; Schuessler, Bryan P; Tellakat, Mohini et al. (2017) Sexually Dimorphic Risk Mitigation Strategies in Rats. eNeuro 4:
Lee, Michael L; Katsuyama, Ângela M; Duge, Leanne S et al. (2016) Fragmentation of Rapid Eye Movement and Nonrapid Eye Movement Sleep without Total Sleep Loss Impairs Hippocampus-Dependent Fear Memory Consolidation. Sleep 39:2021-2031
Pellman, Blake A; Kim, Jeansok J (2016) What Can Ethobehavioral Studies Tell Us about the Brain's Fear System? Trends Neurosci 39:420-431
Pellman, Blake A; Kim, Earnest; Reilly, Melissa et al. (2015) Time-Specific Fear Acts as a Non-Photic Entraining Stimulus of Circadian Rhythms in Rats. Sci Rep 5:14916
Kim, Eun Joo; Park, Mijeong; Kong, Mi-Seon et al. (2015) Alterations of hippocampal place cells in foraging rats facing a ""predatory"" threat. Curr Biol 25:1362-7
Kim, Eun Joo; Pellman, Blake; Kim, Jeansok J (2015) Stress effects on the hippocampus: a critical review. Learn Mem 22:411-6
Lee, Sun-Young; Park, Seong-Hae; Chung, ChiHye et al. (2015) Oxytocin Protects Hippocampal Memory and Plasticity from Uncontrollable Stress. Sci Rep 5:18540

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