Author response: Salient experiences are represented by unique transcriptional signatures in the mouse brain

Can we tell what important event a mouse – or even a person – has recently experienced? The current experience of an individual can be inferred from brain imaging experiments. However, along with changing brain activity, such an experience also switches on gene activity throughout the brain. This enables neurons to produce the proteins required to form a long-term memory of the experience. Do distinct, memorable experiences trigger unique signatures of gene activity? To answer this question, Mukherjee, Ignatowska-Jankowska, Itskovits et al. exposed mice to a variety of experiences. Some were unpleasant and induced aversion; for example, the mouse may have felt nauseous or experienced brief pain and fear. Other experiences, such as when the mouse drank sugary water, received food or was injected with cocaine, were rewarding. Each of the experiences led to the activation of unique combinations of genes in different regions of the brain. Analysing a subset of the activated genes in various brain regions led to the identification of unique and reliable gene expression signatures of experience. These signatures allowed the recent experience of mice to be decoded with nearly 100% accuracy. While these unique signatures can distinguish between recent experiences, experiences that share common features do trigger overlapping patterns of gene activation. For example, negative experiences – but not positive or neutral ones – activated similar patterns of genes in a brain region called the amygdala. In contrast, repeated rewarding experiences induced a distinct gene activity pattern that was most pronounced as increased activity in part of the brain called the frontal cortex. These findings increase our understanding of how the brain represents information. The approach described in the paper provides a strategy to measure the changes in the brain that occur when information is encoded for long-term storage. This measure could also be useful during drug development, revealing how new drug compounds affect the brain, as well as providing an objective measure of the subjective experience of an individual. For example, substances that trigger similar patterns of gene activation to addictive drugs may themselves be addictive. On the other hand, substances that induce similar activity patterns to known medications could also have similar therapeutic properties.

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