Image credit: Kylie Evans (CC BY 4.0)
Post-traumatic stress disorder (or PTSD for short) is a condition that can cause people to overreact to harmless cues, vividly re-experience a traumatic event, or freeze in place. To understand why this happens, researchers often study fear responses using an approach called fear conditioning, where laboratory animals learn to associate the sound of a tone with a mild electric shock. This conditioning causes animals to freeze with fear when they hear the tone.
However, focusing on freezing overlooks the range of defensive actions animals may carry out, such as escaping or fighting. Capturing this complexity in experiments is important for understanding the dynamic nature of fear responses that occur in PTSD. Previous work showed that conditioning mice with a two-part cue, such as a tone followed by white noise, caused mice to freeze during the first cue and jump during the second cue. However, whether the mice learned this behaviour through conditioning or if it was an instinctive response to the cues remained unclear.
To investigate this phenomenon, Le et al. – including some of the researchers involved in the previous work – conditioned mice with a variety of different cue combinations and monitored how they responded. As before, mice conditioned to associate a tone followed by white noise with an electric shock froze when they heard the tone and transitioned to jumping during the white noise. However, if during conditioning the sounds and shocks occurred at unpredictable times, the mice did not associate the sounds with the shock and therefore they froze less and rarely jumped. Similarly, reversing the order of the sounds so that the white noise happened before the tone also reduced jumping but not freezing.
To investigate whether the mice could unlearn this fear response, Le et al. exposed the fear-conditioned mice to the cues without an accompanying electric shock. The mice that had been conditioned with a tone followed by white noise showed a weaker response to the cues, only freezing and not jumping. However, the mice with the reversed cues still froze even after this exposure, and the mice with the non-associated cues maintained very little freezing and jumping.
Taken together, the findings suggest that while fear responses can be influenced by the association between certain noises and an electric shock, other factors such as the timing and the order of the sound cues can also impact the intensity of the fear response. The experiments also showed that this method of fear conditioning can be used for both learning and unlearning fear responses, revealing an approach for future studies into how fear responses change over time. Combining this more complex approach with other experimental techniques could help researchers identify the brain regions that drive fear responses, which may eventually benefit people with PTSD and other fear disorders.
