LAUSR

Significance Rapid changes in neural selectivity have been proposed as a potential mechanism for storing novel associations. Despite this potential mechanism’s being well-recognized in computational models, direct neural evidence is still lacking. Here, we show that characteristic trial-to-trial changes in neural selectivity generated by a working memory model implementing fast Hebbian synaptic plasticity are also present in prefrontal cortex neural populations of monkeys performing a working memory task. Using a trialwise pattern similarity method to track these changes during the encoding of associations, we show that changes in neural selectivity followed the encoding of a new stimulus that breaks down an association between the features of a previous stimulus.