Auditory Cortex Contributes to Threat Memory

Post by Sarah Hill

What's the science?

The same learning principle made famous by Pavlov and his dogs - classical conditioning - is exercised when an animal associates a neutral stimulus with a threat. For example, a mouse that has learned to associate an auditory cue with an impending aversive stimulus (e.g. a foot shock), will exhibit freezing behavior upon hearing the cue even if the cue is no longer followed by a shock. This type of aversive learning results in a threat memory, a form of memory important for future avoidance of aversive stimuli. Whether the auditory cortex, a brain region located in the temporal lobe, is involved in threat memory is unclear, as lesions to this brain region have had mixed effects on memory. This week in Neuron, Dalmay and colleagues show that the auditory cortex and other subregions of the temporal cortex contribute to threat memory acquisition and retrieval.

How did they do it?

The authors used optogenetic methods to inhibit the auditory cortex, and conditioned mice to associate an auditory cue with a foot shock. They carried out both discriminative (i.e. using a conditioned stimulus [CS+] and a neutral stimulus [CS-]) and non-discriminative conditioning (i.e. using only a CS+), presenting one set of animals with complex naturalistic auditory cues (akin to sounds heard in nature) and another with pure tones. To test threat memory, they presented mice the next day with acoustic stimuli, this time without the associated foot shock, and recorded freezing behavior as a measure of the fear response. An analogous series of experiments were then carried out to determine the contribution of neighboring brain areas to threat memory. Optogenetics techniques were similarly used to inhibit adjacent regions of the temporal neocortex, including the ventral region of the secondary auditory cortex, the temporal association cortex, and neuronal axons projecting to the amygdala, the brain region that mediates the fear response. Fear conditioning was again carried out followed by threat memory testing.     

What did they find?

Mice with auditory cortex inhibition exhibited reduced freezing behavior following presentation with complex naturalistic auditory cues, but not after presentation with pure tone cues, suggesting that the role of the auditory cortex in threat memory is dependent on stimulus complexity. This effect was observed whether the auditory cortex was inhibited during fear conditioning or during memory retrieval, as well as in the context of both discriminative and non-discriminative conditioning. Thus, the auditory cortex was shown to contribute in a stimulus-dependent manner to discriminative and non-discriminative threat memory expression. In contrast, mice with inhibition of adjacent temporal cortex regions displayed significant memory impairments regardless of stimulus complexity. Some neocortical subregions were shown to contribute more to threat memory than others — particularly the ventral region of the secondary auditory cortex and the temporal association cortex. Finally, inhibition of amygdala-projecting neurons resulted in reduced freezing behavior when paired with complex, but not pure tone, auditory cues. In other words, complex acoustic stimuli selectively activate direct information transfer between the neocortex and amygdala to elicit auditory threat memory expression.            

What's the impact?

This study conclusively demonstrates a role for the temporal cortex, including the auditory cortex, in auditory threat memory. These findings are particularly important for understanding the extent to which the neocortex participates in learning and memory and the circumstances in which this form of neocortical processing occurs. 

Dalmay et al. A Critical Role for Neocortical Processing of Threat Memory. Neuron (2019). Access the original scientific publication here.