Summary Acetylcholine in the neocortex is critical for executive function. Degeneration of the basal forebrain cholinergic system is associated with cognitive decline in aging and Alzheimer’s disease. Cholinergic agonists and acetylcholinesterase inhibitors improve cognitive performance as does intermittent electrical stimulation of the cortical source of acetylcholine, the Nucleus Basalis (NB) of Meynert. Here we tested how NB stimulation improves working memory behavior and alters its neural code. NB stimulation increased dorsolateral prefrontal activity during the delay period of working memory tasks but did not strengthen phasic responses to the optimal visual stimulus of each neuron. Unexpectedly, improvement of behavioral performance was not the result of increased neural selectivity. Tuning of neuronal responses broadened, which rendered an attractor network more stable and filtered distracting visual stimuli more effectively. Thus, the effects of acetylcholine on prefrontal neural activity and selectivity in working memory contrast those of dopamine and stabilize neural ensembles based on neuromodulatory tone.

Nucleus Basalis Stimulation Enhances Working Memory by Stabilizing Attractor Networks in Prefrontal Cortex