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Science 333 (6044): 888-891

Copyright © 2011 by the American Association for the Advancement of Science

Nicotinic Acetylcholine Receptor β2 Subunits in the Medial Prefrontal Cortex Control Attention

Karine Guillem,1 Bernard Bloem,1,* Rogier B. Poorthuis,1,* Maarten Loos,2 August B. Smit,2 Uwe Maskos,3,4 Sabine Spijker,2,{dagger} Huibert D. Mansvelder1,{dagger},{ddagger}

Abstract: More than one-third of all people are estimated to experience mild to severe cognitive impairment as they age. Acetylcholine (ACh) levels in the brain diminish with aging, and nicotinic ACh receptor (nAChR) stimulation is known to enhance cognitive performance. The prefrontal cortex (PFC) is involved in a range of cognitive functions and is thought to mediate attentional focus. We found that mice carrying nAChR β2-subunit deletions have impaired attention performance. Efficient lentiviral vector–mediated reexpression of functional β2-subunit–containing nAChRs in PFC neurons of the prelimbic area (PrL) completely restored the attentional deficit but did not affect impulsive and motivational behavior. Our findings show that β2-subunit expression in the PrL PFC is sufficient for endogenous nAChR-mediated cholinergic regulation of attentional performance.

1 Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, Netherlands.
2 Department of Molecular and Cellular Neurobiology, CNCR, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, Netherlands.
3 Unité Neurobiologie Intégrative des Systèmes Cholinergiques, Département de Neuroscience, Institut Pasteur, F-75724 Paris cedex 15, France.
4 CNRS, URA2182, F-75724 Paris cedex 15, France.

* These authors contributed equally to this work.

{dagger} These authors contributed equally to this work.

{ddagger} To whom correspondence should be addressed. E-mail: huibert.mansvelder{at}cncr.vu.nl


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