Scientific Understanding of Consciousness
Consciousness as an Emergent Property of Thalamocortical Activity

Attention Control



Science 12 August 2011: Vol. 333 no. 6044 pp. 888-891

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

Karine Guillem1, Bernard Bloem1, Rogier B. Poorthuis1, Maarten Loos2, August B. Smit2, Uwe Maskos3,4, Sabine Spijker2, Huibert D. Mansvelder1

1Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, Netherlands.

2Department of Molecular and Cellular Neurobiology, CNCR, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, Netherlands.

3Unité Neurobiologie Intégrative des Systèmes Cholinergiques, Département de Neuroscience, Institut Pasteur, F-75724 Paris cedex 15, France.

4CNRS, URA2182, F-75724 Paris cedex 15, France.


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.

Cortical acetylcholine (ACh) release from the basal forebrain is essential for proper sensory processing and cognition and tunes neuronal and synaptic activity in the underlying cortical networks. Loss of cholinergic function during aging and Alzheimer’s disease results in cognitive decline, notably a loss of memory and the ability to sustain attention. Interfering with the cholinergic system strongly affects cognition. Rapid changes in prefrontal cortical ACh levels at the scale of seconds are correlated with attending and detecting cues. Various types of nicotinic ACh receptor (nAChR) subunits are expressed in the prefrontal cortex (PFC), and in particular nAChRs containing β2 subunits are thought to enhance attention. However, the causal relation between nAChR β2 subunits (henceforth β2*-nAChRs) expressed in the medial PFC (mPFC) and attention performance has not yet been demonstrated.

Our findings show that expression of β2*-nAChRs is necessary for optimal attentional performance in mice and that restoring expression of β2*-nAChRs in the mPFC PrL area is sufficient for optimal performance. Nicotinic AChRs containing β2 subunits are located on cell bodies of neurons as well as on thalamocortical afferents in the PrL PFC, which have been suggested to be involved in attention and processing of sensory stimuli. The present study reveals that restoration of β2*-nAChR receptors, specifically in the PrL area of the mPFC, is sufficient to restore the attentional deficit of β2−/− mice to WT levels. Attentional control therefore appears to be mediated by endogenous ACh acting on β2*-nAChR receptors expressed by neurons located within the PrL mPFC, although a role for β2*-nAChRs on thalamic projections cannot be entirely excluded on the basis of the present results. Nevertheless, the nAChR system in the PrL mPFC is a principal factor in attentional control. Consistent with this, rapid changes of ACh levels in mPFC are correlated with cue attending and detection, an effect mainly due to mPFC    β2*-nAChRs stimulation. Our findings have implications relevant for understanding the neurobiology of attention and suggest agonists or positive allosteric modulators at these mPFC    β2*-nAChRs within the PrL   PFC as potential targets for the development of more effective treatments for cognitive impairments.

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