Intermittent rate coding and cue-specific ensembles support working memory

Persistent, memorandum-specific neuronal spiking activity has long been hypothesized to underlie working memory1,2. However, emerging evidence suggests a potential role for ‘activity-silent’ synaptic mechanisms3–5. This issue remains controversial because evidence for either view has largely relied either on datasets that fail to capture single-trial population dynamics or on indirect measures of neuronal spiking. We addressed this controversy by examining the dynamics of mnemonic information on single trials obtained from large, local populations of lateral prefrontal neurons recorded simultaneously in monkeys performing a working memory task. Here we show that mnemonic information does not persist in the spiking activity of neuronal populations during memory delays, but instead alternates between coordinated ‘On’ and ‘Off’ states. At the level of single neurons, Off states are driven by both a loss of selectivity for memoranda and a return of firing rates to spontaneous levels. Further exploiting the large-scale recordings used here, we show that mnemonic information is available in the patterns of functional connections among neuronal ensembles during Off states. Our results suggest that intermittent periods of memorandum-specific spiking coexist with synaptic mechanisms to support working memory.