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    Influence of developmental nicotine exposure on glutamatergic neurotransmission in rhythmically active hypoglossal motoneurons

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    Author
    Cholanian, Marina
    Powell, Gregory L.
    Levine, Richard B.
    Fregosi, Ralph F.
    Affiliation
    Department of Physiology, University of Arizona College of Medicine
    Department of Neuroscience, University of Arizona
    Issue Date
    2017-01
    Keywords
    AMPA
    Breathing
    Glutamate
    Hypoglossal nucleus
    Nicotine
    Desensitization
    
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    Publisher
    ACADEMIC PRESS INC ELSEVIER SCIENCE
    Citation
    Influence of developmental nicotine exposure on glutamatergic neurotransmission in rhythmically active hypoglossal motoneurons 2017, 287:254 Experimental Neurology
    Journal
    Experimental Neurology
    Rights
    © 2016 Elsevier Inc. All rights reserved.
    Collection Information
    This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
    Abstract
    Developmental nicotine exposure (DNE) is associated with increased risk of cardiorespiratory, intellectual, and behavioral abnormalities in neonates, and is a risk factor for apnea of prematurity, altered arousal responses and Sudden Infant Death Syndrome. Alterations in nicotinic acetylcholine receptor signaling (nAChRs) after DNE lead to changes in excitatory neurotransmission in neural networks that control breathing, including a heightened excitatory response to AMPA microinjection into the hypoglossal motor nucleus. Here, we report on experiments designed to probe possible postsynaptic and presynaptic mechanisms that may underlie this plasticity. Pregnant dams were exposed to nicotine or saline via an osmotic mini-pump implanted on the 5th day of gestation. We used whole-cell patch clamp electrophysiology to record from hypoglossal motoneurons (XIIMNs) in thick medullary slices from neonatal rat pups (N = 26 control and 24 DNE cells). To enable the translation of our findings to breathing-related consequences of DNE, we only studied XIIMNs that were receiving rhythmic excitatory drive from the respiratory central pattern generator. Tetrodotoxin was used to isolate XIIMNs from presynaptic input, and their postsynaptic responses to bath application of L-glutamic acid (glutamate) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) were studied under voltage clamp. DNE had no influence on inward current magnitude evoked by either glutamate or AMPA. However, in cells from DNE animals, bath application of AMPA was associated with a right shift in the amplitude distribution (P = 0.0004), but no change in the inter-event interval distribution of miniature excitatory postsynaptic currents (mEPSCs). DNE had no influence on mEPSC amplitude or frequency evoked by glutamate application, or under (unstimulated) baseline conditions. Thus, in the presence of AMPA, DNE is associated with a small but significant increase in quantal size, but no change in the probability of glutamate release.
    Note
    12 month embargo; Available online 29 July 2016
    ISSN
    00144886
    PubMed ID
    27477858
    DOI
    10.1016/j.expneurol.2016.07.023
    Version
    Final accepted manuscript
    Sponsors
    National Institutes of Health [R01 HD071302]
    Additional Links
    http://linkinghub.elsevier.com/retrieve/pii/S0014488616302229
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.expneurol.2016.07.023
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