Neural Dynamics of Fear Circuits in Ecological Rodent Models of Risk and Trauma

University Of Washington, Seattle WA

Investigators

Abstract

PROJECT SUMMARY For over a century, Pavlovian fear conditioning paradigms have been pivotal in studying basic associative fear memory formation through conditioned stimulus (CS) pathways, significantly enhancing our understanding of fear- and anxiety-related disorders in humans. However, given that the brain's fear system may operate differently under real-world risks, it is essential to explore neural dynamics and behavioral outcomes within ecologically relevant scenarios. This application proposes to utilize our established 'approach food-avoid predator' paradigm in rats to investigate the primary fear circuit mechanisms involved in risky decision-making within spatial environments featuring lifelike agents of danger. This approach leverages how the biologically-primed innate or unconditioned stimulus (US) pathways process and adapt to potential and actual attacks. Aim 1: We will test the hypothesis that the amygdala functions as a pivotal relay, processing biological threat information from the midbrain and transmitting fear signals to specific corticolimbic structures, thereby guiding risky goal-directed decisions. This investigation will thoroughly examine the dynamics of predatory pathways among the periaqueductal gray, amygdala, hippocampus, and medial prefrontal cortex, spanning anatomical, neurophysiological, and causal dimensions. Aim 2: We will characterize the changes in midbrain-corticolimbic mechanisms resulting from a singular life-and- death event—a nociceptive shock to the dorsal neck/body during evasion from a predatory threat—that cause generalized, nonassociative fear responses. These observations could yield insights into post-trauma-like avoidance behaviors. Our research has dual significance. Firstly, it enhances foundational knowledge from fear conditioning paradigms that emphasize CS pathway-mediated learned fear responses by offering a broader perspective on fear mechanisms incorporating US pathway-mediated innate and nonassociative fear responses. Secondly, it integrates dynamic agent-induced trauma perspectives relevant to interpersonal threat conditions. This comprehensive approach holds the potential to advance treatments for trauma disorders, particularly those stemming from assaults.