We use the active place avoidance paradigm to investigate the neurobiological basis of memory and cognitive control because the paradigm is one of the most sensitive assays for hippocampus function in rodents. Mice and rats show task deficits after virtually any manipulation designed to disrupt hippocampus function, including partial and unilateral inactivation of hippocampus, ischemic stroke, silencing or ablation of adult born granule cells, and manipulation of synaptic plasticity molecular function.
However, especially in reviews of our grants and those of colleagues, the active place avoidance task is assumed to be stressful and a form of fear conditioning. Unlike the water maze, inhibitory avoidance, and fear conditioning paradigms that are more commonly used to study the neurobiology of memory, active place avoidance is minimally stressful. In prior work, we have not been able to distinguish animals trained in the task from controls that never receive or avoid shock, using behavior and defecation as measures of responses to stress and fear. That work seems to not have convinced many in the community, who may be more familiar with the far more intense shock of other memory paradigms, and not appreciate how mild a 500 ms 0.2-0.3 mA shock feels.
In Edith's new paper we tried to address this concern of the community by measuring the stress hormone corticosterone in mice across learning the standard version of the active place avoidance task. Corticosterone levels were no different from control animals that explored the environment without receiving shock. Hopefully, this evidence will be compelling and allow the community to more accurately assess data collected within the paradigm, without the interpretational bias that can come from assumptions that are not supported by evidence, despite their intuitive appeal. As a final note, we always try to rely on experimental design, to control for factors we do not know, which is why depending on the question being addressed, we sometimes use untrained subjects or yoked-shock subjects to compare to subjects that perform active place avoidance.
Thank you Edith and the team for pulling together to hopefully clarify this issue for the community!