Journal
CEREBRAL CORTEX
Volume 16, Issue 1, Pages 9-17Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhi079
Keywords
acetylcholine; attention; prefrontal cortex; basal forebrain; microdialysis
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Funding
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH063114, K02MH001072] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS037026] Funding Source: NIH RePORTER
- NIMH NIH HHS [MH63114, K02 MH01072] Funding Source: Medline
- NINDS NIH HHS [NS37026] Funding Source: Medline
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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.
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