title: Plasticity of prefrontal attention circuitry: upregulated muscarinic excitability in response to decreased nicotinic signaling following deletion of α5 or β2 subunits.
abstract: Attention depends on cholinergic stimulation of nicotinic and muscarinic acetylcholine receptors in the medial prefrontal cortex. Pyramidal neurons in layer VI of this region express cholinergic receptors of both families and play an important role in attention through their feedback projections to the thalamus. Here, we investigate how nicotinic and muscarinic cholinergic receptors affect the excitability of these neurons using whole-cell recordings in acute brain slices of prefrontal cortex. Since attention deficits have been documented in both rodents and humans having genetic abnormalities in nicotinic receptors, we focus in particular on how the cholinergic excitation of layer VI neurons is altered by genetic deletion of either of two key nicotinic receptor subunits, the accessory α5 subunit or the ligand-binding β2 subunit. We find that the cholinergic excitation of layer VI neurons is dominated by nicotinic receptors in wild-type mice and that the reduction or loss of this nicotinic stimulation is accompanied by a surprising degree of plasticity in excitatory muscarinic receptors. These findings suggest that disrupting nicotinic receptors fundamentally alters the mechanisms and timing of excitation in prefrontal attentional circuitry.
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Ontario M5S1A8, Canada.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Tian
authors.forename: Craig D C
authors.initials: CD
authors.lastname: Bailey
authors.forename: Mariella
authors.initials: M
authors.lastname: De Biasi
authors.forename: Marina R
authors.initials: MR
authors.lastname: Picciotto
authors.forename: Evelyn K
authors.initials: EK
authors.lastname: Lambe
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009538:Nicotine / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000494:pharmacology; D000068797:Orexins; D018408:Patch-Clamp Techniques / Q000379:methods; D017397:Prefrontal Cortex / Q000166:cytology*; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000172:deficiency*; D015398:Signal Transduction / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D000109:Acetylcholine; D000157:Aconitine; D001285:Atropine; D004079:Dihydro-beta-Erythroidine; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D009538:Nicotine; D018733:Nicotinic Antagonists; D000068797:Orexins; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; C523972:CHRNA5 protein, mouse; C054634:methyllycaconitine
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