Plasticity of Persistent Activity and Its Constraints.

Stimulus information is maintained in working memory by action potentials that persist after the stimulus is no longer physically present. The prefrontal cortex is a critical brain area that maintains such persistent activity due to an intrinsic network with unique synaptic connectivity, NMDA receptors, and interneuron types. Persistent activity can be highly plastic depending on task demands but it also appears in naïve subjects, not trained or required to perform a task at all. Here, we review what aspects of persistent activity remain constant and what factors can modify it, focusing primarily on neurophysiological results from non-human primate studies. Changes in persistent activity are constrained by anatomical location, with more ventral and more anterior prefrontal areas exhibiting the greatest capacity for plasticity, as opposed to posterior and dorsal areas, which change relatively little with training. Learning to perform a cognitive task for the first time, further practicing the task, and switching between learned tasks can modify persistent activity. The ability of the prefrontal cortex to generate persistent activity also depends on age, with changes noted between adolescence, adulthood, and old age. Mean firing rates, variability and correlation of persistent discharges, but also time-varying firing rate dynamics are altered by these factors. Plastic changes in the strength of intrinsic network connections can be revealed by the analysis of synchronous spiking between neurons. These results are essential for understanding how the prefrontal cortex mediates working memory and intelligent behavior.