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.

Tuning and playing a motor rhythm: how metabotropic glutamate receptors orchestrate generation of motor patterns in the mammalian central nervous system.

Repeated motor activities like locomotion, mastication and respiration need rhythmic discharges of functionally connected neurons termed central pattern generators (CPGs) that cyclically activate motoneurons even in the absence of descending commands from higher centres. For motor pattern generation, CPGs require integration of multiple processes including activation of ion channels and transmitter receptors at strategic locations within motor networks. One emerging mechanism is activation of glutamate metabotropic receptors (mGluRs) belonging to group I, while group II and III mGluRs appear to play an inhibitory function on sensory inputs.

Glutamate uptake block triggers deadly rhythmic bursting of neonatal rat hypoglossal motoneurons.

In the brain the extracellular concentration of glutamate is controlled by glial transporters that restrict the neurotransmitter action to synaptic sites and avoid excitotoxicity. Impaired transport of glutamate occurs in many cases of amyotrophic lateral sclerosis, a devastating motoneuron disease. Motoneurons of the brainstem nucleus hypoglossus are among the most vulnerable, giving early symptoms like slurred speech and dysphagia.

Metabotropic glutamate receptor activity induces a novel oscillatory pattern in neonatal rat hypoglossal motoneurones.

Tongue muscles innervated by the hypoglossal nerves play a crucial role to ensure airway patency and milk suckling in the neonate. Using a slice preparation of the neonatal rat brain, we investigated the electrophysiological characteristics of hypoglossal motoneurones in the attempt to identify certain properties potentially capable of synchronizing motor commands to the tongue. Bath-applied DHPG, a selective agonist of group I metabotropic glutamate receptors (mGluRs), generated persistent, regular electrical oscillations (4-8 Hz) recorded from patch-clamped motoneurones.

Activation of group I metabotropic glutamate receptors enhances efficacy of glutamatergic inputs to neonatal rat hypoglossal motoneurons in vitro.

Group I metabotropic glutamate receptors (mGluRs) are the main class of metabotropic receptors expressed in the hypoglossus nucleus. Their role in glutamatergic transmission was investigated using patch-clamp recording from motoneurons in a neonatal rat brainstem slice preparation. After pharmacological block of gamma-aminobutyric acid and glycine-mediated inhibition, under voltage-clamp, the selective group I agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) induced a motoneuron inward current by depressing a leak conductance, and strongly facilitated spontaneous glutamatergic synaptic currents.