Sharifullina E, Ostroumov K, Grandolfo M, Nistri A
N-methyl-d-aspartate triggers neonatal rat hypoglossal motoneurons in vitro to express rhythmic bursting with unusual Mg(2+) sensitivity. [JOURNAL ARTICLE]
Neuroscience 2008 Mar 19.
The brainstem nucleus hypoglossus innervates the tongue which must contract rhythmically during respiration, chewing and swallowing. Such rhythmic discharges are due to network bursting mediated by AMPA receptor-dependent glutamatergic transmission. The contribution by hypoglossal motoneurons themselves to rhythmicity remains, however, unclear as they might simply express cyclic patterns produced by premotoneurons or, in analogy to spinal motoneurons, might participate to bursting due to activation of their N-methyl-d-aspartate (NMDA) receptors. Using patch clamp recording from hypoglossal motoneurons in slice preparations of neonatal rat brainstem, we observed that NMDA directly depolarized motoneurons to generate various discharge patterns. Most motoneurons produced transient bursts which were consistently restored by repolarizing membrane potential to rest. Fewer motoneurons generated either sustained bursting or random firing. Rhythmic bursts were recorded from XII nerve rootlets even when single motoneuron bursting required hyperpolarization. NMDA evoked bursts were blocked by the Ca(2+) antagonist Cd(2+), the gap junction blocker carbenoxolone, or Mg(2+) free solution, and partially inhibited by tetrodotoxin or nifedipine. Under voltage clamp, NMDA-induced bursting persisted at negative or positive potentials and was resistant to high extracellular Mg(2+) in accordance with the observation of widespread motoneuron expression of NMDA 2D receptor subunits that confer poor Mg(2+) sensitivity. It is proposed that NMDA depolarized motoneurons with the contribution of Mg(2+) insensitive channels, and triggered bursting via cyclic activation/deactivation of voltage-dependent Na(+), Ca(2+) and K(+) currents spread through gap junctions. The NMDA-evoked bursting pattern was similar to the rhythmic discharges previously recorded from the XII nerve during milk sucking by neonatal rats.
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