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Authors & Affiliations
Harry Robson, Livia Wilod Versprille, Clara Velazquez-Sanchez, Matthew Bailey, Olivia Stupart, Johann du Hoffmann, Jeff Dalley
Abstract
Cholinergic dysfunction contributes to attentional deficits in attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and dementia. Cortical cholinergic inputs are fundamentally linked to attention and phasic acetylcholine (Ach) release causally mediates performance in tasks involving monitoring for cues, cue detection, and cue-directed responding.We investigated the role of muscarinic and nicotinic ACh receptors (mAChRs and nAChRs) in attentional performance by applying systemic manipulations in adult male and female Sprague-Dawley rats during the Signal Detection Task. In this task, rats detect and respond to the absence or presence of visual light to obtain food reward. Outcome measures included accuracy, response latencies, sensitivity, response bias, and the probability of a given trial resulting in a “shift hit” (hits preceded by actual or perceived non-signal events, thus requiring shifts from monitoring to cue detection and response). Dose-dependency was established using a Latin square design with a 48-hour washout between each compound.The mAChR antagonist, scopolamine, impaired accuracy, response latencies, and shift hit probability, but failed to impair sensitivity or response bias. Conversely, the nAChR antagonist, mecamylamine, impaired accuracy, response latencies, shift hit probability, as well as sensitivity and bias. The M4 AChR positive allosteric modulator (PAM), VU0467154, had no effect on the outcome measures. The alpha-7 nAChR PAM, CCMI, had no effect on accuracy, sensitivity, or bias, but did accelerate correct response latency.These findings suggest differential roles of nicotinic and muscarinic receptors during fast, accurate performance in attentional tasks involving signal detection, and may inform the development of cholinergic interventions for attentional deficits in patients.