title: Influence of developmental nicotine exposure on glutamatergic neurotransmission in rhythmically active hypoglossal motoneurons.
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 α-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.
authors.affiliation: Department of Physiology, University of Arizona College of Medicine, Tucson, AZ 85724, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Cholanian
authors.affiliation: Department of Physiology, University of Arizona College of Medicine, Tucson, AZ 85724, USA.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Powell
authors.affiliation: Department of Physiology, University of Arizona College of Medicine, Tucson, AZ 85724, USA; Department of Neuroscience, University of Arizona, Tucson, AZ 85724, USA.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Levine
authors.affiliation: Department of Physiology, University of Arizona College of Medicine, Tucson, AZ 85724, USA; Department of Neuroscience, University of Arizona, Tucson, AZ 85724, USA. Electronic address: fregosi@email.arizona.edu.
authors.forename: Ralph F
authors.initials: RF
authors.lastname: Fregosi
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D004347:Drug Interactions; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D007002:Hypoglossal Nerve / Q000166:cytology* / Q000254:growth & development; D066298:In Vitro Techniques; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology; D008564:Membrane Potentials / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D018722:Nicotinic Agonists; D026941:Sodium Channel Blockers; D018698:Glutamic Acid; D013779:Tetrodotoxin; D009538:Nicotine
keywords: AMPA; Breathing; Desensitization; Glutamate; Hypoglossal nucleus; Nicotine