Stimulus Salience Determines the Defensive Behaviors Elicited by Aversively Conditioned Compound Auditory Stimuli

Abstract

SUMMARYAnimals exhibit distinct patterns of defensive behavior according to their perceived imminence of potential threats. Ethoexperimental [1, 2] and aversive conditioning [3-5] studies indicate that as the probability of directly encountering a threat increases, animals shift from behaviors aimed at avoiding detection (e.g. freezing) to escape (e.g. undirected flight). What are the neural mechanisms responsible for assessing threat imminence and controlling appropriate behavioral responses? Fundamental to addressing these questions has been the development of behavioral paradigms in mice in which well-defined threat-associated sensory stimuli reliably and robustly elicit passive or active defensive responses [6, 7]. In serial compound stimulus (SCS) fear conditioning, repeated pairing of sequentially presented tone (CS1) and white noise (CS2) auditory stimuli with footshock (US) yields learned freezing and flight responses to CS1 and CS2, respectively [6]. Although this white noise-induced transition from freezing to flight would appear to reflect increased perceived imminence due to the US being more temporally proximal to CS2 than CS1, this model has not been directly tested. Surprisingly, we find that audio frequency properties and sound pressure levels, not temporal relationship to the US, determine the defensive behaviors elicited by SCS conditioned auditory stimuli. Notably, auditory threat stimuli that most potently elicit high imminence behaviors include frequencies to which mouse hearing is most sensitive. These results argue that, as with visual threats [8], perceived imminence and resulting intensity of defensive responses scale with the salience of auditory threat stimuli.