Asymmetrical stimulus generalization following differential fear conditioning

Abstract

Rodent ultrasonic vocalizations (USVs) are ethologically critical social signals. Rats emit 22 kHz USVs and 50 kHz USVs, respectively, in conjunction with negative and positive affective states. Little is known about what controls emotional reactivity to these social signals. Using male SpragueDawley rats, we examined unconditional and conditional freezing behavior in response to the following auditory stimuli: three 22 kHz USVs, a discontinuous tone whose frequency and on-off pattern matched one of the USVs, a continuous tone with the same or lower frequencies, a 4 kHz discontinuous tone with an on-off pattern matched to one of the USVs, and a 50 kHz USV. There were no differences among these stimuli in terms of the unconditional elicitation of freezing behavior. Thus, the stimuli were equally neutral before conditioning. During differential fear conditioning, one of these stimuli (the CS + ) always co-terminated with a footshock unconditional stimulus (US) and another stimulus (the CS − ) was explicitly unpaired with the US. There were no significant differences among these cues in CS + -elicited freezing behavior. Thus, the stimuli were equally salient or effective as cues in supporting fear conditioning. When the CS + was a 22 kHz USV or a similar stimulus, rats discriminated based on the principal frequency and/or the temporal pattern of the stimulus. However, when these same stimuli served as the CS − , discrimination failed due to generalization from the CS + . Thus, the stimuli differed markedly in the specificity of conditioning. This strikingly asymmetrical stimulus generalization is a novel bias in discrimination.

Rats concatenate 22 kHz and 50 kHz calls into a single utterance

“…Similar to alarm calls in other mammals (Mateo and Holmes, 1997), 22 kHz calls in rats are not innately recognized as a distress signal (e.g. Wöhr and Schwarting, 2010;Endres et al, 2007;Bang et al, 2008) and 50 kHz vocal patterns are also influenced by experience (Wöhr et al, 2008).…”

“…In anticipation of pain or danger, rats often produce long bouts of calls in the 19-28 kHz range with little or no frequency modulation, which are referred to as '22 kHz calls'. The playback of 22 kHz calls causes freezing behavior (Endres et al, 2007;Allen et al, 2007;Bang et al, 2008;Kim et al, 2010;Parsana et al, 2012a,b). Vocalizations with fundamental frequencies between 28 and 90 kHz are collectively referred to as '50 kHz calls'.…”

Zinc transporter 3 is involved in learned fear and extinction, but not in innate fear

“…The deficiency in the training protocol using one shock is likely to be based on disturbances of function in the lateral nucleus of the amygdala, since Zn 2+ and ZnT3 are present there at high levels. Recent work has demonstrated that the perirhinal cortex is involved in the processing of learned fear for context as well as trace conditioning, discontinuous tones, ultrasound vocalizations, and "complex auditory objects" (Campeau and Davis 1995;Corodimas and LeDoux 1995;Bucci et al 2000;Lindquist et al 2004;Bang et al 2008;Kholodar-Smith et al 2008b;Bang and Brown 2009). It is therefore possible that the deficiency in fear processing in ZnT3 KO mice, when a discontinuous tone is used, is based at least in part on improper function of the perirhinal cortex.…”

Discriminative Auditory Fear Learning Requires Both Tuned and Nontuned Auditory Pathways to the Amygdala

“…As we are interested in general mechanisms of discrimination we chose to avoid frequencies that are close to the ones used in social communication. Furthermore, it has been shown that rats trained in a differential CS ϩ /CS Ϫ AFC protocol tend to generalize their fear responses toward 22 kHz tones, which corresponds to the fundamental frequency of alarm calls (Bang et al, 2008). Thus, the frequency of the CS ϩ was chosen to be the 10 kHz frequency (which is closer to the 22 kHz principal frequency), to avoid biasing our results toward generalization, which may arise from responses to USVs and innate fear.…”