title: The nicotinic acetylcholine receptor alpha5 subunit plays a key role in attention circuitry and accuracy.
abstract: 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.
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Craig D C
authors.initials: CD
authors.lastname: Bailey
authors.forename: Mariella
authors.initials: M
authors.lastname: De Biasi
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Fletcher
authors.forename: Evelyn K
authors.initials: EK
authors.lastname: Lambe
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001288:Attention / Q000187:drug effects / Q000502:physiology*; D002755:Choice Behavior / Q000502:physiology; D018678:Cholinergic Agents / Q000494:pharmacology; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009415:Nerve Net / Q000502:physiology; D009483:Neuropsychological Tests; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D010775:Photic Stimulation / Q000379:methods; D017397:Prefrontal Cortex / Q000166:cytology; D017966:Pyramidal Cells / Q000502:physiology*; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D011978:Receptors, Nicotinic / Q000172:deficiency / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000109:Acetylcholine; D000779:Anesthetics, Local; D018678:Cholinergic Agents; D004079:Dihydro-beta-Erythroidine; D009538:Nicotine; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; C523972:CHRNA5 protein, mouse