title: Early postnatal nicotine exposure disrupts the α2* nicotinic acetylcholine receptor-mediated control of oriens-lacunosum moleculare cells during adolescence in rats.
abstract: Maternal cigarette smoking during pregnancy and maternal nicotine exposure in animal models are associated with cognitive impairments in offspring. However, the underlying mechanism remains unknown. Oriens-lacunosum moleculare (OLM) cells expressing α2* nicotinic acetylcholine receptors (nAChRs) are an important component of hippocampal circuitry, gating information flow and long-term potentiation (LTP) in the CA1 region. Here we investigated whether early postnatal nicotine exposure alters the normal role of α2*-nAChR-expressing OLM cells during adolescence in rats. We found that early postnatal nicotine exposure significantly decreased not only the number of α2-mRNA-expressing interneurons in the stratum oriens/alveus, but also α2*-nAChR-mediated responses in OLM cells. These effects of nicotine were prevented by co-administration with the nonselective nAChR antagonist mecamylamine, suggesting that nicotine-induced activation, but not desensitization, of nAChRs mediates the effects. α2*-nAChR-mediated depolarization of OLM cells normally triggers action potentials, causing an increase in spontaneous inhibitory postsynaptic currents in synaptically connected pyramidal cells. However, these α2*-nAChR-mediated effects were profoundly reduced after early postnatal nicotine exposure, suggesting altered control of CA1 circuits by α2*-nAChR-expressing OLM cells. Furthermore, these effects were associated with altered excitatory neural activity and LTP as well as the loss of normal α2*-nAChR-mediated control of excitatory neural activity and LTP. These findings suggest the altered function of α2*-nAChR-expressing OLM cells as an important target of further study for identifying the mechanisms underlying the cognitive impairment induced by maternal smoking during pregnancy.
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-4550, USA.
authors.forename: Kang
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-4550, USA.
authors.forename: Sakura
authors.initials: S
authors.lastname: Nakauchi
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-4550, USA.
authors.forename: Hailing
authors.initials: H
authors.lastname: Su
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-4550, USA.
authors.forename: Saki
authors.initials: S
authors.lastname: Tanimoto
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-4550, USA. Electronic address: ksumikaw@uci.edu.
authors.forename: Katumi
authors.initials: K
authors.lastname: Sumikawa
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects* / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011810:Quinoxalines; C056723:FG 9041; D009538:Nicotine; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine; D001640:Bicuculline
keywords: Development; Hippocampus; LTP; Nicotine; OLM cells; α2 nicotinic acetylcholine receptor