Activation and desensitization of neuronal nicotinic receptors modulate glutamatergic transmission on neonatal rat hypoglossal motoneurons.
In the neonate the muscles of the tongue, which are exclusively innervated by the XII cranial nerves originating from the brainstem nucleus hypoglossus, must contract rhythmically in coincidence with breathing, suckling and swallowing. These motor commands are generated by hypoglossal motoneurons excited by glutamatergic inputs. Because in forebrain areas the efficiency of glutamatergic transmission is modulated by neuronal nicotinic receptors (nAChRs), the role and identity of nAChRs within the nucleus hypoglossus of the neonatal rat were explored using an in vitro brainstem slice preparation. This area expressed immunoreactivity for alpha4, alpha7 and beta2 nAChR subunits. Whole-cell patch-clamp recording from hypoglossal motoneurons showed lack of spontaneous cholinergic events mediated by nAChRs even in the presence of a cholinesterase inhibitor. However, pharmacological antagonism of alpha7- or beta2-containing receptors depressed glutamatergic currents arising either spontaneously or by electrical stimulation of the reticular formation. Hypoglossal motoneurons expressed functional nAChRs with characteristics of alpha4beta2 and alpha7 receptor subunits. Such receptors underwent fast desensitization (time constant of 200 ms) with full recovery within 1 min. Low (0.5 microm) concentration of nicotine first facilitated glutamatergic transmission on motoneurons and later depressed it through receptor desensitization. When 0.1 microm nicotine was used, only depression of synaptic transmission occurred, in keeping with the suggestion that nAChRs can be desensitized without prior activation. These results highlight the role of tonic nAChR activity in shaping excitatory inputs to hypoglossal motoneurons, and suggest that nAChR desensitization by ambient nicotine could contribute to disorders of tongue muscle movements.
Quitadamo
Costanza
C
Neurobiology Sector and CNR-INFM Unit, International School for Advanced Studies (SISSA), Via Beirut 4, 34014 Trieste, Italy.
Fabbretti
Elsa
E
Lamanauskas
Nerijus
N
Nistri
Andrea
A
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D015153:Blotting, Western; D001933:Brain Stem / Q000502:physiology; D004594:Electrophysiology; D005455:Fluorescent Antibody Technique; D005971:Glutamates / Q000502:physiology*; D007002:Hypoglossal Nerve / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009046:Motor Neurons / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D005971:Glutamates; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D009538:Nicotine