Developmental nicotine exposure alters synaptic input to hypoglossal motoneurons and is associated with altered function of upper airway muscles

Lila Buls Wollman, Jordan Clarke, Claire M. Delucia, Richard B. Levine, Ralph F. Fregosi

Research output: Contribution to journalArticle

Abstract

Nicotine exposure during the fetal and neonatal periods [developmental nicotine exposure (DNE)] is associated with ineffective upper airway protective reflexes in infants. This could be explained by desensitized chemore-ceptors and/or mechanoreceptors, diminished neuromuscular transmission or altered synaptic transmission among central neurons, as each of these systems depend in part on cholinergic signaling through nicotinic AChRs (nAChRs). Here, we showed that DNE blunts the response of the genioglossus (GG) muscle to nasal airway occlusion in lightly anesthetized rat pups. The GG muscle helps keep the upper airway open and is innervated by hypoglossal motoneurons (XIIMNs). Experiments using the phrenic nerve-diaphragm preparation showed that DNE does not alter transmission across the neuromuscular junction. Accordingly, we used whole cell recordings from XIIMNs in brainstem slices to examine the influence of DNE on glutamatergic synaptic transmission under baseline conditions and in response to an acute nicotine challenge. DNE did not alter excitatory transmission under baseline conditions. Analysis of cumulative probability distributions revealed that acute nicotine challenge of P1–P2 preparations resulted in an increase in the frequency of nicotine-induced glutamatergic inputs to XIIMNs in both control and DNE. By contrast, P3–P5 DNE pups showed a decrease, rather than an increase in frequency. We suggest that this, together with previous studies showing that DNE is associated with a compensatory increase in inhibitory synaptic input to XIIMNs, leads to an excitatory-inhibitory imbalance. This imbalance may contribute to the blunting of airway protective reflexes observed in nicotine exposed animals and human infants.

Original languageEnglish (US)
Article numberENEURO.0299-19.2019
JournaleNeuro
Volume6
Issue number6
DOIs
StatePublished - Nov 1 2019

Keywords

  • Motor neuron
  • Nicotine
  • Perinatal
  • Plasticity
  • Synaptic transmission
  • Whole cell recording

ASJC Scopus subject areas

  • Neuroscience(all)

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