A repertoire of rhythmic bursting produced by hypoglossal motoneurons in physiological and pathological conditions.
The brainstem nucleus hypoglossus contains motoneurons that provide the exclusive motor nerve supply to the tongue. In addition to voluntary tongue movements, tongue muscles rhythmically contract during a wide range of physiological activities, such as respiration, swallowing, chewing and sucking. Hypoglossal motoneurons are destroyed early in amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease often associated with a deficit in the transport system of the neurotransmitter glutamate. The present study shows how periodic electrical discharges of motoneurons are mainly produced by a neuronal network that drives them into bursting mode via glutamatergic excitatory synapses. Burst activity is, however, modulated by the intrinsic properties of motoneurons that collectively synchronize their discharges via gap junctions to create 'group bursters'. When glial uptake of glutamate is blocked, a distinct form of pathological bursting spontaneously emerges and leads to motoneuron death. Conversely, H(2)O(2)-induced oxidative stress strongly increases motoneuron excitability without eliciting bursting. Riluzole (the only drug currently licensed for the treatment of ALS) suppresses bursting of hypoglossal motoneurons caused by blockage of glutamate uptake and limits motoneuron death. These findings highlight how different patterns of electrical oscillations of brainstem motoneurons underpin not only certain physiological activities, but also motoneuron death induced by glutamate transporter impairment.
Cifra
Alessandra
A
International School for Advanced Studies (SISSA), Via Beirut 2-4, 34014 Trieste, Italy.
Nani
Francesca
F
Sharifullina
Elina
E
Nistri
Andrea
A
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001933:Brain Stem / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007002:Hypoglossal Nerve / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000503:physiopathology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010507:Periodicity; D019782:Riluzole / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014059:Tongue / Q000294:innervation / Q000502:physiology*
D018696:Neuroprotective Agents; D018698:Glutamic Acid; D019782:Riluzole; D006861:Hydrogen Peroxide