title: Early postnatal nicotine exposure causes hippocampus-dependent memory impairments in adolescent mice: Association with altered nicotinic cholinergic modulation of LTP, but not impaired LTP.
abstract: Fetal nicotine exposure from smoking during pregnancy causes long-lasting cognitive impairments in offspring, yet little is known about the mechanisms that underlie this effect. Here we demonstrate that early postnatal exposure of mouse pups to nicotine via maternal milk impairs long-term, but not short-term, hippocampus-dependent memory during adolescence. At the Schaffer collateral (SC) pathway, the most widely studied synapses for a cellular correlate of hippocampus-dependent memory, the induction of N-methyl-D-aspartate receptor-dependent transient long-term potentiation (LTP) and protein synthesis-dependent long-lasting LTP are not diminished by nicotine exposure, but rather unexpectedly the threshold for LTP induction becomes lower after nicotine treatment. Using voltage sensitive dye to visualize hippocampal activity, we found that early postnatal nicotine exposure also results in enhanced CA1 depolarization and hyperpolarization after SC stimulation. Furthermore, we show that postnatal nicotine exposure induces pervasive changes to the nicotinic modulation of CA1 activity: activation of nicotinic receptors no longer increases CA1 network depolarization, acute nicotine inhibits rather than facilitates the induction of LTP at the SC pathway by recruiting an additional nicotinic receptor subtype, and acute nicotine no longer blocks LTP induction at the temporoammonic pathway. These findings reflect the pervasive impact of nicotine exposure during hippocampal development, and demonstrate an association of hippocampal memory impairments with altered nicotinic cholinergic modulation of LTP, but not impaired LTP. The implication of our results is that nicotinic cholinergic-dependent plasticity is required for long-term memory formation and that postnatal nicotine exposure disrupts this form of plasticity.
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, 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, Irvine, CA 92697-4550, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Malvaez
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, 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, Irvine, CA 92697-4550, USA.
authors.forename: Elise
authors.initials: E
authors.lastname: Kleeman
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697-4550, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Dang
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697-4550, USA.
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Wood
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, 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; D001007:Anxiety / Q000139:chemically induced; D005260:Female; D006624:Hippocampus / Q000187:drug effects*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects*; D009538:Nicotine / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000633:toxicity*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D021641:Recognition, Psychology / Q000187:drug effects; D065852:Spatial Memory / Q000187:drug effects
chemical_list: D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D009538:Nicotine
keywords: CA1 region; Object location memory; Object recognition memory; Schaffer collateral pathway; Temporoammonic pathway