Thinking outside the conditioning box: ethological paradigms for studying fear, anxiety and risky decision-making in rodents

Abstract

Traditional behavioral neuroscience paradigms assessing fear, anxiety and risky decision-making in rodents typically utilize restrictive environments that severely limit the animal’s behavioral repertoire. Additionally, such paradigms take a hyper-focused approach by studying few behavioral variables over brief periods, effectively producing “snapshots” of neurobehavioral phenomena. Finally, these paradigms largely ignore animals’ innate fear and anxiety-related behavior toward non pain-inducing environmental stimuli and instead commonly rely on conditioned stimuli to instigate defensive behavior. Ethological paradigms of fear, anxiety and risky decision-making, which seek to engender naturalistic scenarios within a laboratory setting, rectify many of these limitations by providing goal-directed tasks in more permissive environments, examining both innate and conditioned fear/anxiety-related behavior, studying the brain and behavior across a wider timescale and by studying many variables (a holistic approach). This dissertation presents specific experiments conducted in ethological paradigms of fear, anxiety and risky decision-making in both rats and mice that exemplify the utility and advantages of ethological paradigms as a whole. First introduced is the longitudinal, semi-naturalistic “Risky Closed Economy” paradigm (RCE). The first study details how the RCE can be used to comprehensively investigate the impact of chronic threat on day-to-day behavior in mice. The following study conducted in rats shows how the holistic approach afforded by the RCE can facilitate interpretation of nuclei function; specifically, it is shown that the lateral habenula participates in appetitive behavior involving natural reinforcers (food pellets) and not approach-avoidance conflict involving chronic, unpredictable threat. Lastly, the “Approach Food-Avoid Predator” paradigm (AFAP) is introduced; an ethological foraging paradigm that simulates predator-prey interaction. The final study covered shows how the AFAP produces a unique neural signature of fear and risky decision-making in mice relative to standard fear conditioning and innate fear paradigms lacking naturalistic approach-avoidance conflict.