The Risky Closed Economy: A Holistic, Longitudinal Approach to Studying Fear and Anxiety in Rodents

Abstract

Basic research of fear and anxiety in rodents has historically utilized a limited set of behavioral paradigms, for example, Pavlovian (classical) fear conditioning, the elevated plus-maze, or inhibitory (passive) avoidance. These traditional paradigms measure a limited selection of variables over a short duration, providing only a "snapshot" of fear and anxiety-related behavior. Overreliance on these paradigms and such behavioral snapshots ultimately lead to a narrow understanding of these complex motivational states. Here, we elaborate on the closed economy; a seldom-used paradigm that has been modified to comprehensively study fear and anxiety-related behavior and neurocircuitry in rodents. In this modified "Risky Closed Economy (RCE)" paradigm, animals live nearly uninterrupted in behavioral chambers where the need to acquire food and water and avoid threat is integrated into the task. Briefly, animals are free to acquire all of their food and water in a designated foraging zone. An unsignaled, unpredictable threat (footshock) is introduced into the foraging zone after a baseline activity and consumption period to model the risk of predation, which is then removed for a final extinction assessment. This longitudinal design, wherein data from a multitude of variables are collected automatically and continuously for 23 h/day over several weeks to months, affords a more holistic understanding of the effects of fear and anxiety on day-today behavior. Also, we discuss its general benefits relevant to other topics in neuroscience research, its limitations, and present data demonstrating for the first time The Risky Closed Economy's viability in mice.

Commentary: The Risky Closed Economy: A Holistic, Longitudinal Approach to Studying Fear and Anxiety in Rodents

“…The Risky Closed Economy: A Holistic, Longitudinal Approach to Studying Fear and Anxiety in Rodents by Schuessler, B. P., Zambetti, P. R., Kukuoka, K. M., Kim, E. J., and Kim, J. J. (2020).…”

“…As a result, many experimental tasks have been developed to delve deeper into the neural basis of fear learning. Through a comprehensive review of the most popular paradigms for rodents, recent work by Schuessler et al ( 2020 ) discusses the potential of the “Risky Closed Economy” (RCE) as a more realistic and holistic paradigm to study fear and anxiety. While previously employed in rats (Helmstetter and Fanselow, 1993 ; Kim et al, 2014 ; Pellman et al, 2015 ), the authors also explore a possible adaptation of the RCE for mice.…”

“…Another advantageous consequence of the RCE setup is that experiments can be implemented over significantly larger time scales. While fear conditioning experiments usually span only from minutes to a few hours (Pellow et al, 1985 ; Maren, 2008 ), Schuessler et al ( 2020 ) were able to monitor mice behavior 23 h/day for 7 weeks. The longer autonomy given to animals helps minimize observer-expectancy effects, as experimenters only intervened for daily health checks.…”

“…Although the RCE has only been previously applied to rats (Helmstetter and Fanselow, 1993 ; Kim et al, 2014 ; Pellman et al, 2015 ), Schuessler et al ( 2020 ) showed that it can also be adapted to mice. That development will likely open up more research opportunities, in particular making optogenetics experiments easier and drug testing more efficient.…”

Cross-species anxiety tests in psychiatry: pitfalls and promises

“…A number of potential reasons for this stagnation have been prominently discussed. The first is the narrow scope of anxiety tests in relation to biological scenarios [3,4], and their conceptual inadequacy in relation to clinical conditions [5][6][7]. However, even if the tests were conceptually adequate, behavioural control might still differ substantially between species as disparate as rodents and humans, which diverge in many aspects of their neurobiology, from receptor distribution to macroscopic structure of the neocortex [8], and ensuing human-specific cognition [9,10].…”