The nicotinic acetylcholine receptor alpha5 subunit plays a key role in attention circuitry and accuracy.

Stimulation of the prefrontal cortex by acetylcholine is critical for attention; however, the cellular mechanisms underlying its influence on attention pathways within the brain are not well understood. Pyramidal neurons in layer VI of the prefrontal cortex are believed to play an important role in this process because they are excited by acetylcholine and provide a major source of feedback projections to the thalamus. Here, we show using whole-cell electrophysiology that the relatively rare alpha5 subunit of the nicotinic acetylcholine receptor powerfully enhances nicotinic currents in layer VI pyramidal neurons in prefrontal cortical brain slices from adult mice. In addition, behavioral experiments using the five-choice serial reaction time test show that the presence of the nicotinic receptor alpha5 subunit also increases the accuracy of adult mice on this visual attention task under highly demanding conditions. Together, these findings demonstrate a novel and important role for the nicotinic receptor alpha5 subunit in adult brain circuitry required for attentional performance.