Abstract
Cholinergic neuromodulation is known to play a key role in visual working memory (VWM) – keeping relevant stimulus representations available for cognitive processes up to a few minutes. Despite the growing body of evidence on how the neural and cognitive mechanisms of working memory dynamically change over retention time, studies that measure cholinergic effects as a function of time in non-human primates has been scarce. Using the delayed matching to sample (DMTS) VWM task in rhesus macaques (N=6), we studied how cholinergic neuromodulation influences VWM maintenance across a wide range of delays (1 to 72 s). We aimed at disentangling which delay intervals are most affected by transient amnestic treatments using the muscarinic receptor antagonist scopolamine administered alone and in combination with two doses of the clinically widely used acetylcholinesterase inhibitor (AChEI) donepezil, probing for the reversal of scopolamine-induced impairments. Results indicate that scopolamine-induced impairments of VWM maintenance are delay-dependent and specifically affect the 10-30 seconds time range, suggesting that scopolamine speeds up the normal deterioration of VWM with the passage of time. Donepezil partially rescued the scopolamine-induced impairments of VWM performance. These results are in line with our current knowledge on the role of muscarinic acetylcholine receptors in the maintenance of working memory. Taking delay length into account can be a valuable component of basic and preclinical pharmacological research on the behavioral manifestations of VWM maintenance and can deepen our current understanding of short-term memory and its age-related impairments.
Abbreviations
- ACh
- Acetylcholine
- AD
- Alzheimer’s disease
- NHP
- Non-human primate
- SCOP
- scopolamine
- DON
- donepezil
- VWM
- visual working memory