title: Postsynaptic nicotinic acetylcholine receptors facilitate excitation of developing CA1 pyramidal neurons.
abstract: The hippocampus plays a key role in learning and memory. The normal development and mature function of hippocampal networks supporting these cognitive functions depends on afferent cholinergic neurotransmission mediated by nicotinic acetylcholine receptors. Whereas it is well-established that nicotinic receptors are present on GABAergic interneurons and on glutamatergic presynaptic terminals within the hippocampus, the ability of these receptors to mediate postsynaptic signaling in pyramidal neurons is not well understood. We use whole cell electrophysiology to show that heteromeric nicotinic receptors mediate direct inward currents, depolarization from rest and enhanced excitability in hippocampus CA1 pyramidal neurons of male mice. Measurements made throughout postnatal development provide a thorough developmental profile for these heteromeric nicotinic responses, which are greatest during the first 2 wk of postnatal life and decrease to low adult levels shortly thereafter. Pharmacological experiments show that responses are blocked by a competitive antagonist of α4β2* nicotinic receptors and augmented by a positive allosteric modulator of α5 subunit-containing receptors, which is consistent with expression studies suggesting the presence of α4β2 and α4β2α5 nicotinic receptors within the developing CA1 pyramidal cell layer. These findings demonstrate that functional heteromeric nicotinic receptors are present on CA1 pyramidal neurons during a period of major hippocampal development, placing these receptors in a prime position to play an important role in the establishment of hippocampal cognitive networks.
authors.affiliation: Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada; and.
authors.forename: Beryl Y T
authors.initials: BY
authors.lastname: Chung
authors.affiliation: Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada; and.
authors.forename: Warren
authors.initials: W
authors.lastname: Bignell
authors.affiliation: Department of Psychology, College of Social and Applied Human Sciences, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Derek L
authors.initials: DL
authors.lastname: Jacklin
authors.affiliation: Department of Psychology, College of Social and Applied Human Sciences, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Boyer D
authors.initials: BD
authors.lastname: Winters
authors.affiliation: Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada; and baileyc@uoguelph.ca.
authors.forename: Craig D C
authors.identifier: 0000-0002-4320-6872
authors.initials: CD
authors.lastname: Bailey
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000254:growth & development*; D005260:Female; D051379:Mice; D011247:Pregnancy; D017966:Pyramidal Cells / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000502:physiology*; D055366:Synaptic Potentials / Q000502:physiology*
chemical_list: D011978:Receptors, Nicotinic
keywords: CA1 pyramidal neuron; brain development; electrophysiology; hippocampus; nicotinic receptor