50 years of mnemonic persistent activity: quo vadis?

Half a century ago persistent spiking activity in the neocortex was discovered to be a neural substrate of working memory. Since then scientists have sought to understand this core cognitive function across biological and computational levels. Studies are reviewed here that cumulatively lend support to a synaptic theory of recurrent circuits for mnemonic persistent activity that depends on various cellular and network substrates and is mathematically described by a multiple-attractor network model. Crucially, a mnemonic attractor state of the brain is consistent with temporal variations and heterogeneity across neurons in a subspace of population activity. Persistent activity should be broadly understood as a contrast to decaying transients. Mechanisms in the absence of neural firing ('activity-silent state') are suitable for passive short-term memory but not for working memory - which is characterized by executive control for filtering out distractors, limited capacity, and internal manipulation of information.