Developmental nicotine exposure enhances inhibitory synaptic transmission in motor neurons and interneurons critical for normal breathing

Dev Neurobiol. 2016 Mar;76(3):337-54. doi: 10.1002/dneu.22318. Epub 2015 Jun 29.


Nicotine exposure in utero negatively affects neuronal growth, differentiation, and synaptogenesis. We used rhythmic brainstems slices and immunohistochemistry to determine how developmental nicotine exposure (DNE) alters inhibitory neurotransmission in two regions essential to normal breathing, the hypoglossal motor nucleus (XIIn), and preBötzinger complex (preBötC). We microinjected glycine or muscimol (GABAA agonist) into the XIIn or preBötC of rhythmic brainstem slices from neonatal rats while recording from XII nerve roots to obtain XII motoneuron population activity. Injection of glycine or muscimol into the XIIn reduced XII nerve burst amplitude, while injection into the preBötC altered nerve burst frequency. These responses were exaggerated in preparations from DNE animals. Quantitative immunohistochemistry revealed a significantly higher GABAA receptor density on XII motoneurons from DNE pups. There were no differences in GABAA receptor density in the preBötC, and there were no differences in glycine receptor expression in either region. Nicotine, in the absence of other chemicals in tobacco smoke, alters normal development of brainstem circuits that are critical for normal breathing.

Keywords: GABA; brainstem slice; glycine; hypoglossal motoneurons; preBötzinger complex.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Excitatory Postsynaptic Potentials / drug effects
  • Female
  • Immunohistochemistry
  • Interneurons / drug effects*
  • Male
  • Motor Neurons / drug effects*
  • Nicotine / toxicity*
  • Nicotinic Agonists / toxicity*
  • Organ Culture Techniques
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Center / drug effects*
  • Synaptic Transmission / drug effects*


  • Nicotinic Agonists
  • Nicotine