Cholinergic neuromodulation of prefrontal attractor dynamics controls performance in spatial working memory.

Acetylcholine has been thought to improve cognitive performance by sharpening neuronal tuning in prefrontal cortex. Recent work has shown that electrical stimulation of the cholinergic forebrain in awake-behaving monkeys induces a reduction in prefrontal neural tuning under stimulation conditions that improve performance. To reconcile these divergent observations, we provide network simulations showing that these derive consistently from specific conditions in prefrontal attractor dynamics: firing rate saturation leads to increased storage precision and reduced neural tuning upon cholinergic activation via an increase in neural excitability, a reduction in neural correlations, and an increase in excitatory transmission. Our study integrates previously reported data into a consistent mechanistic view of how acetylcholine controls spatial working memory via attractor network dynamics in prefrontal cortex.