Cholinergic Mechanisms of Target Oddball Stimuli Detection: The Late "P300-Like" Event-Related Potential in Rats.

A. Ahnaou,W. H. I. M. Drinkenburg,R. Biermans

doi:10.1155/2018/4270263

A. Ahnaou, W. H. I. M. Drinkenburg + Show 1 more

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https://doi.org/10.1155/2018/4270263

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Abstract

Event-related potentials (ERPs) and oscillations (EROs) provide powerful tools for studying the brain's synaptic function underlying information processing. The P300 component of ERPs indexing attention and working memory shows abnormal amplitude and latency in neurological and psychiatric diseases that are sensitive to pharmacological agents. In the active auditory oddball discriminant paradigm, behavior and auditory-evoked potentials (AEPs) were simultaneously recorded in awake rats to investigate whether P300-like potentials generated in rats responding to rare target oddball tones are sensitive to subcutaneous modulation of the cholinergic tone by donepezil (1 mg/kg) and scopolamine (0.64 mg/kg). After operant training, rats consistently discriminate rare target auditory stimuli from frequent irrelevant nontarget auditory stimuli by a higher level of correct lever presses (i.e., accuracy) in target trials associated with a food reward. Donepezil attenuated the disruptive effect of scopolamine on the level of accuracy and premature responses in target trials. Larger P300-like peaks with early and late components were revealed in correct rare target stimuli trials as compared to frequent tones. Donepezil enhanced the peak amplitude of the P300-like component to target stimuli and evoked slow theta and gamma oscillations, whereas scopolamine altered the amplitude of the P300-like component and EROs to target stimuli. Pretreatment with donepezil attenuated effects of scopolamine on the peak amplitude of the P300-like component and on EROs. This study provides evidence that AEP P300-like responses can be elicited by rats engaged in attentive and memory processing of target stimuli and outline the relevance of the cholinergic system in stimulus discrimination processing. The findings highlight the sensitivity of this translational index for investigating brain circuits and/or novel pharmacological agents, which modulate cholinergic transmission associated with increased allocation of attentional resources.

Highlights

Despite the recent flurry of research efforts in contemporary cognitive neuroscience, there remains a need to identify an early biomarker with high sensitivity and specificity for cognitive impairments
In the active auditory oddball discriminant paradigm, behavior and auditory-evoked potentials (AEPs) were simultaneously recorded in awake rats to investigate whether P300-like potentials generated in rats responding to rare target oddball tones are sensitive to subcutaneous modulation of the cholinergic tone by donepezil (1 mg/kg) and scopolamine (0.64 mg/kg)
Donepezil enhanced the peak amplitude of the P300-like component to target stimuli and evoked slow theta and gamma oscillations, whereas scopolamine altered the amplitude of the P300-like component and event-related oscillations (EROs) to target stimuli

Summary

Introduction

Despite the recent flurry of research efforts in contemporary cognitive neuroscience, there remains a need to identify an early biomarker with high sensitivity and specificity for cognitive impairments. Many cognitive functions are unique to humans and cannot be addressed in experimental animals whilst cognitive paradigms and models must have translational validity to be of use in drug discovery. Despite the availability of some level of face and construct validity for assays and disease models used in cognition research, the critical feature for drug discovery is the predictive validity [1,2,3]. Ideal animal models of cognition should provide a prediction of the specific conditions for which compounds would be most useful and could be combined with toxicology and safety pharmacology models to estimate the therapeutic effect [4]. Focus on brain neuronal circuits and connectivity is a promising approach to provide a closer link between animal models and the disorders they model [5,6,7,8,9]

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