Developmental Nicotine Exposure Results in Exaggerated Response to AMPA Receptor Activation in Hypoglossal Motoneurons in Neonatal Rats

Abstract

Nicotine is the primary neurotoxin in tobacco products, as it has been strongly associated with altered development of neurons throughout the brain, including brainstem neurons involved in the control of breathing. Chronic nicotine exposure causes widespread desensitization of nicotinic acetylcholine receptors (nAChRs), leading to increased receptor expression, but a reduction in synaptic efficacy. Our previous work in rhythmically active hypoglossal motoneurons (XIIMNs) showed that developmental nicotine exposure (DNE) desensitizes their nAChRs and reduces excitatory synaptic input to these cells. We also showed that expression of somatic glutamate receptors was reduced, suggesting a reduction in post‐synaptic efficacy. Here we hypothesize that DNE results in increased postsynaptic responses to AMPA receptor activation in XIIMNs from neonatal rats. Whole cell voltage clamp recordings of rhythmically active XIIMNs in brainstem slices from control and DNE animals were made. AMPA (2.5 mM) was bath‐applied in the presence of TTX to isolate fast postsynaptic glutamatergic responses. Preliminary data suggest a larger AMPA‐mediated inward current and a higher charge transfer in DNE XIIMNs (DNE, n = 10; control, n = 12). All responses were blocked by CNQX (20 mM), a selective AMPA and kainate receptor antagonist, indicating that the responses were AMPAergic. These results indicate that DNE: (1) upregulates AMPA receptor expression in XIIMNs, and/or (2) changes the kinetics of AMPA receptors in order to overcome the reduced excitatory synaptic input to XIIMNs.