AbstractGeneralized fear is one purported mechanism of anxiety that is a target of clinical and basic research. Impaired fear discrimination has been primarily examined from the perspective of increased fear learning, rather than how learning about non-threatening stimuli affects fear discrimination. To address this question, we tested how three Safety Conditioning protocols with varied levels of salience allocated to the safety cue compared to classic Fear Conditioning in their impact on subsequent innate anxiety, and differential fear learning of new aversive and neutral cues. Using a high anxiety strain of mice (129SvEv, Taconic), we show that Fear Conditioned animals show little exploration of the anxiogenic center of an open field 24 hours later, and poor discrimination during new differential conditioning 7 days later. Three groups of mice underwent Safety Conditioning, (i) the safety tone was unpaired with a shock, (ii) the safety tone was unpaired with the shock and co-terminated with a house light signaling the end of the safety period, and (iii) the safety tone was unpaired with the shock and its beginning co-occurred with a house light, signaling the start of a safety period. Mice from all Safety Conditioning groups showed higher levels of open field exploration than the Fear Conditioned mice 24 hours after training. Furthermore, Safety Conditioned animals showed improved discrimination learning of a novel non-threat, with the Salient Beginning safety conditioned group performing best. These findings indicate that high anxiety animals benefit from salient safety training to improve exploration and discrimination of new non-threating stimuli.HighlightsSafety training using salient cues improves safety learning in high anxiety miceSalient Safety training improves novel fear discrimination learningSafety training improves exploration in a novel anxiogenic environment
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