Neuronal activity in sensory cortex predicts the specificity of learning

Learning to avoid dangerous signals while preserving normal responses to safe stimuli is essential for everyday behavior and survival. Fear learning has a high level of inter-subject variability. Following identical experiences, subjects exhibit fear specificities ranging from high (specializing fear to only the dangerous stimulus) to low (generalizing fear to safe stimuli). Pathological fear generalization underlies emotional disorders, such as post-traumatic stress disorder. The neuronal basis of fear specificity remains unknown. Here, we identified the neuronal code that underlies inter-subject variability in fear specificity using longitudinal imaging of neuronal activity before and after differential fear conditioning in the auditory cortex of mice. Neuronal activity prior to, but not after learning predicted the level of specificity following fear conditioning across subjects. Stimulus representation in auditory cortex was reorganized following conditioning. However, the reorganized neuronal activity did not relate to the specificity of learning. These results present a novel neuronal code that determines individual patterns in learning.