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. Since 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 a4, a7 and b2 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 a7 or b2 containing receptors depressed glutamatergic currents arising either spontaneously or by electrical stimulation of the reticular formation. Hypoglossal motoneurons expressed functional nAChRs with characteristics of a4b2 and a7 receptor subunits, and displaying fast desensitization (time constant of 200 ms) from which full recovery developed within one min. Low (0.5 µM) concentration of nicotine first facilitated glutamatergic transmission on motoneurons and later depressed it through receptor desensitization. When 0.1 µM 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 their desensitization by ambient nicotine could contribute to disorders of tongue muscle movements.
|Autori:||Quitadamo, Maria Costanza|
|Titolo:||Neuronal nicotinic receptors modulate glutamatergic transmission on neonatal rat hypoglossal motoneurons|
|Data di pubblicazione:||19-set-2005|
|Appare nelle tipologie:||8.1 PhD thesis|