title: Functional alpha7 nicotinic receptors are expressed on immature granule cells of the postnatal dentate gyrus.
abstract: Neurogenesis occurs throughout life in the subgranular zone of the dentate gyrus, and postnatal-born granule cells migrate into the granule cell layer and extend axons to their target areas. The α7*nicotinic receptor has been implicated in neuronal maturation during development of the brain and is abundant in interneurons of the hippocampal formation of the adult brain. Signalling through these same receptors is believed also to promote maturation and integration of adult-born granule cells in the hippocampal formation. We therefore aimed to determine whether functional α7*nicotinic receptors are expressed in developing granule cells of the postnatal dentate gyrus. For these experiments we used 2-3 week-old Wistar rats, and 2-9 week old transgenic mice in which GABAergic interneurons were marked by expression of green fluorescent protein. Immunohistochemistry indicated the presence of α7*nicotinic receptor subunits around granule cells close around the subgranular zone which correlated with the distribution of developmental markers for immature granule cells. Whole-cell patch clamp recording showed that a proportion of granule cells responded to puffed ACh in the presence of atropine, and that these cells possessed electrophysiological properties found in immature granule cells. The nicotinic responses were potentiated by an allosteric α7*nicotinic receptor modulator, which were blocked by a specific α7*nicotinic receptor antagonist and were not affected by ionotropic glutamate or GABA receptor antagonists. These results suggest the presence of functional somato-dendritic α7*nicotinic receptors on immature granule cells of the postnatal dentate gyrus, consistent with studies implicating α7*nicotinic receptors in dendritic maturation of dentate gyrus neurons in adult brain.
authors.affiliation: School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK. Electronic address: djohn@ucsd.edu.
authors.forename: Danielle
authors.initials: D
authors.lastname: John
authors.affiliation: Department of Molecular Basis of Neurosignaling, Laboratory of Molecular Toxinology, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow V-437, Russia.
authors.forename: Irina
authors.initials: I
authors.lastname: Shelukhina
authors.affiliation: Department of Genetic and Behavioural Neuroscience, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan; Japan Science and Technology Agency, CREST, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
authors.forename: Yuchio
authors.initials: Y
authors.lastname: Yanagawa
authors.affiliation: School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Jim
authors.initials: J
authors.lastname: Deuchars
authors.affiliation: School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Zaineb
authors.initials: Z
authors.lastname: Henderson
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000906:Antibodies; D018679:Cholinergic Agonists / Q000494:pharmacology; D018891:Dentate Gyrus / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D059330:GABAergic Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007395:Interneurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats; D017208:Rats, Wistar; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000276:immunology / Q000378:metabolism / Q000502:physiology*
chemical_list: D000906:Antibodies; D018679:Cholinergic Agonists; D064569:alpha7 Nicotinic Acetylcholine Receptor; D000109:Acetylcholine
keywords: Alpha 7 nicotinic acetylcholine receptors; Dentate gyrus; Neurogenesis