decreased the CD8z T cell population clinical development of therapies in these challenging disorders

In our daily lives, we are often confronted with decisions that require weighing each option’s costs against its associated benefits. Disturbances in such cost/benefit decision making have been reported in populations of virtually every severe neuropsychiatric illness, and can adversely affect the day-to-day lives of these individuals. Thus, laboratory models of decision making have been developed to characterize these deficits in humans and identify putative neurobiological mechanisms, while animal models have allowed researchers to test the causative relationships between neural circuitry, neurochemistry, and choice. These studies have yielded considerable converging data on contributions of cortico-limbic-striatal brain regions, as well as neuromodulatory influences, on decision making. Alterations in central cholinergic function underlie both the etiology and treatment of a number of illnesses in which decision making is perturbed, including Alzheimer’s disease, attentiondeficit/hyperactivity disorder, and schizophrenia. Interestingly, the most commonly reported cholinergic-driven improvements are within the attentional domain, a cognitive process long associated with central acetylcholine. While recent studies have examined cholinergic contributions to decision making under risk and delay via multiple drugs, and while one cholinergic agonist has been used to study effort-based decision making, whether acetylcholine regulates decision making with attentional effort costs has yet to be investigated. As such, it is unclear whether treatments that have a beneficial effect on attention per se would also have a beneficial effect on choices related to those demand costs. Relatedly, cigarette smokers often claim that nicotine enhances their mental focus and performance, but such effects may be limited to specific cognitive domains or relevant only to a subsection of individuals. Our group has recently validated a rodent Cognitive Effort Task, wherein animals can choose to allocate greater visuospatial attention for a greater reward, and this task provides measures of both attentional performance and choice based on attentional demand. Previous work with this task GSK212 871700-17-3 indicates that the neurochemical regulation of willingness to work can be dissociated from ability, and that baseline differences in the degree to which animals choose to apply cognitive effort to earn greater rewards is a key determinant of drug response. For example, the psychostimulant amphetamine caused hard-working animals to “slack off”, i.e. choose a greater proportion of trials with lower attentional demands, while “slacker” animals worked harder in response to the drug in the absence of any change in attentional accuracy. The rCET is thus uniquely situated to dissociate acetylcholine’s influence on decision making under attentional costs from acetylcholine’s impact on attentional performance. The goal of this study was therefore to examine how nicotinic and muscarinic acetylcholine.

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