Augmented Prefrontal Acetylcholine Release during Challenged Attentional Performance

Abstract

Previous research has demonstrated that attentional performance depends on the integrity of the cortical cholinergic input system and that such performance is associated with increases in cortical acetylcholine (ACh) release. The present experiment tested the hypothesis that the attentional impairments produced by bilateral basal forebrain infusions of the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV) are associated with attenuation of performance-associated increases in ACh release. Rats were trained in a sustained attention task and equipped with three guide cannula for the bilateral infusion of the NMDA receptor antagonist APV (0, 3, 20 nmol) and for the insertion of a dialysis probe into the medial prefrontal cortex (mPFC). APV or vehicle was infused remotely following completion of the first of five blocks of trials. During the first block, attentional performance was associated with a 140% increase in ACh efflux. Infusions of APV decreased the animals' ability to detect signals and augmented the increases in ACh efflux observed prior to infusions. These data indicate a dissociation between levels of attentional performance and increases in mPFC ACh release. Augmentation of performance-associated increases in mPFC cholinergic transmission is hypothesized to mediate the increased demands on attentional 'effort' that are required to maintain performance under challenging conditions.

Toward a Neuro-Cognitive Animal Model of the Cognitive Symptoms of Schizophrenia: Disruption of Cortical Cholinergic Neurotransmission Following Repeated Amphetamine Exposure in Attentional Task-Performing, but Not Non-Performing, Rats

“…Thus, the effects of repeated AMPH exposure and AMPH-challenge on ACh release did not differ between the two collections taken before task onset and the four collections taken during task performance (see Figure 4). Similar to the results from previous experiments (Arnold et al, 2002;Himmelheber et al, 2000;Kozak et al, 2006), performance of the attention task increased ACh release in the mPFC over baseline. In SAL/SAL animals, ACh release increased by 158.28718.49% over basal ACh levels during the performance of the task (F(1,6) ¼ 66.98; po0.001; see Figure 4).…”

“…Removal of cortical cholinergic inputs produces persistent impairments in attentional performance. Furthermore, attentional performance is associated with increases in cortical acetylcholine (ACh) release that are not observed in animals performing tasks controlling for the nonattentional aspects of performance (Dalley et al, 2001;Himmelheber et al, 1997Himmelheber et al, , 2000Kozak et al, 2006;McGaughy et al, 1996McGaughy et al, , 2000Passetti et al, 2000;Sarter, 1997, 2000). The available evidence indicates that the cortical cholinergic input system mediates not one particular aspect of attention but supports a range of attentional abilities, including sustained, selective, and divided attention.…”

Abnormal Neurotransmitter Release Underlying Behavioral and Cognitive Disorders: Toward Concepts of Dynamic and Function-Specific Dysregulation

“…Contrasting effects on release were found in animals performing a task, which taxes attentional functions and is known to depend on the integrity and activity of the cortical cholinergic input system (Arnold et al, 2002;McGaughy et al, 1996). Specifically, in task-performing animals, blockade of these same ionotropic glutamate receptors resulted in the augmentation of the increases in transmitter release normally observed as a function of task performance (Kozak et al, 2006a). Thus, the effects of the pharmacological manipulation on neurotransmitter release were diametrically different depending on the stimulus (general activational stimulus vs task performance) employed to recruit the neurotransmitter system.…”

Towards a muscarinic hypothesis of schizophrenia

“…In understanding the function of acetylcholine in the brain, a special emphasis has been placed on the importance of acetylcholine for memory and learning 26,27 with a focus on a specific role of the cholinergic forebrain system in attention. 21,28 A deficit in the function of the cholinergic system is thus likely to result in cognitive impairment. As neurocognitive impairment is frequently associated with schizophrenia, 1,2 and has been shown to be worsened by exposure to muscarinic antagonists, 29,30 an involvement of the cholinergic system in the pathophysiology of this illness seems possible.…”