Chronic nicotinic exposure decreases the synaptic strength of nAChR‐mediated glutamatergic input onto neonatal hypoglossal motoneurons

Abstract

Although nicotinic acetylcholine receptors (nAChRs) are widespread in the CNS their role in the control of breathing is still unclear. This study aims to test the hypothesis that alterations in nAChRs, evoked by chronic nAChR excitation, impairs respiratory‐related neurotransmission onto hypoglossal motoneurons (HMN) that control the tongue. To test our hypothesis we used rhythmic medullary slice preparations and simultaneously recorded from both single respiratory modulated HMN and whole hypoglossal nerve rootlets on day 1–4 in rat pups chronically exposed to nicotine or saline in utero and during the first week of life. Results show that synaptic strength, predominately glutamatergic, was decreased but without changes in the frequency of respiratory rhythm determined by the respiratory central pattern generator (CPG). The average number of spontaneous excitatory postsynaptic potentials (EPSPs), measured during the “expiratory” period, was decreased 42% (P < 0.05), but their magnitude was unchanged. Furthermore, EPSPs could be abolished by bath application of AMPAergic antagonist 6‐cyano‐7‐nitroquinoxaline‐2, 3‐dione (CNQX). These results show that the chronic in utero exposure to nicotine decreases excitatory neurotransmission at HMN synapses and suggests that this change results from frequency of nAChR‐mediated presynpatic release of glutamate. Funded by NIH #1R03HD061613‐01.