Guillem_2011_Science_333_888

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 beta2-subunit deletions have impaired attention performance. Efficient lentiviral vector-mediated reexpression of functional beta2-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 beta2-subunit expression in the PrL PFC is sufficient for endogenous nAChR-mediated cholinergic regulation of attentional performance.