Abstract
Executive functions are an emerging propriety of neuronal processing in circuits encompassing frontal cortex and other cortical and subcortical brain regions such as basal ganglia and thalamus. Glutamate serves as the major neurotrasmitter in these circuits where glutamate receptors of NMDA type play key role. Serotonin and dopamine afferents are in position to modulate intrinsic glutamate neurotransmission along these circuits and in turn to optimize circuit performance for specific aspects of executive control over behavior. In this review, we focus on the 5-choice serial reaction time task which is able to provide various measures of attention and executive control over performance in rodents and the ability of prefrontocortical and striatal serotonin 5-HT1A, 5-HT2A, and 5-HT2C as well as dopamine D1- and D2-like receptors to modulate different aspects of executive and attention disturbances induced by NMDA receptor hypofunction in the prefrontal cortex. These behavioral studies are integrated with findings from microdialysis studies. These studies illustrate the control of attention selectivity by serotonin 5-HT1A, 5-HT2A, 5-HT2C, and dopamine D1- but not D2-like receptors and a distinct contribution of these cortical and striatal serotonin and dopamine receptors to the control of different aspects of executive control over performance such as impulsivity and compulsivity. An association between NMDA antagonist-induced increase in glutamate release in the prefrontal cortex and attention is suggested. Collectively, this review highlights the functional interaction of serotonin and dopamine with NMDA dependent glutamate neurotransmission in the cortico-striatal circuitry for specific cognitive demands and may shed some light on how dysregulation of neuronal processing in these circuits may be implicated in specific neuropsychiatric disorders.
Highlights
The integrated activity across frontal cortex and other cortical and sub-cortical brain regions supports a number of cognitive processes subsumed under the term “executive function.” These cognitive processes comprise: selective allocation of attentional resources, maintenance, retrieval, and manipulation of information in working memory, formulation and planning of appropriate sequences of actions, inhibition of inappropriate responses and decision-making on the basis of positive or negative outcomes
It is apparent that the input selection process of attention and executive control over impulsive and perseverative responding may be the results of integration of N-methyl D-aspartate (NMDA) receptor function and the activity in 5-HT and DA receptor systems along the nodes of cortico-striatal circuitry
The reviewed studies show that these deficits are differentially responsive to pharmacological manipulations of 5-HT and DA receptor activity in the medial PFC (mPFC) and dorsomedial striatum (dm-STR) and that increased cortical glutamate release and cortico-striatal transmission is associated with impaired attention but not with enhanced impulsivity and perseverative responding
Summary
We focus on the 5-choice serial reaction time task which is able to provide various measures of attention and executive control over performance in rodents and the ability of prefrontocortical and striatal serotonin 5-HT1A, 5-HT2A, and 5-HT2C as well as dopamine D1- and D2-like receptors to modulate different aspects of executive and attention disturbances induced by NMDA receptor hypofunction in the prefrontal cortex. These behavioral studies are integrated with findings from microdialysis studies.
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