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

Abstract

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. Under voltage clamp, oscillations were biphasic events, comprising large outward slow currents alternated with fast, repeated inward currents. Electrical oscillations had amplitude and period insensitive to cell membrane potential, and required intact glutamatergic transmission via AMPA receptors. Oscillations were mediated by subtype 1 receptors of group I mGluRs (mGluR1s), and were routinely observed during pharmacological block of glycinergic and GABAergic inhibition, although they could also be recorded in standard saline. Simultaneous recordings from pairs of motoneurones within the same hypoglossal nucleus demonstrated that oscillations were due to their strong electrical coupling and were blocked by the gap junction blocker carbenoxolone. Pacing of slow oscillations apparently depended on the operation of K ATP channels in view of the block by tolbutamide or glibenclamide. Under current clamp, oscillations generated more regular spike firing of motoneurones and facilitated glutamatergic excitatory inputs. These data suggest that neonatal motoneurones of the nucleus hypoglossus possess a formerly undisclosed ability to express synchronous electrical oscillations, unveiled by activation of mGluR1s.

Contribution of motoneuron intrinsic properties to fictive motor pattern generation

“…For example, studies have shown that there is electrical coupling between hypoglossal motoneurons associated with breathing (Rekling et al 2000) and tongue movements (Sharifullina et al 2005) as well as among motoneurons in Xenopus embryos (Perrins and Roberts 1995). Furthermore, when gap junctions were blocked in Xenopus embryos, Zhang et al (2009) noted that the burst durations of motoneurons increased, resulting in alteration of rostro-caudal delays during fictive swimming.…”

A repertoire of rhythmic bursting produced by hypoglossal motoneurons in physiological and pathological conditions

“…Bursting is apparently paced by the cyclic activation of K ATP conductances, thus linking electrical discharges to the cell energy metabolism. Current clamp recording indicates that, during bursting, motoneuron spikes appear only at the peak of each burst, in contrast to the irregular firing emerging when the same cell is depolarized to a comparable level of membrane potential (Sharifullina et al 2005). Hence, bursts strongly constrain the firing pattern of motoneurons and amplify AMPA receptor-mediated synaptic inputs.…”

“…To sum up, hypoglossal motoneurons can produce rhythmic bursting elicited by NMDA through a robust mechanism that is mainly intrinsic to these cells because it is unaffected by blockers of excitatory Bursts are observed as inward current (large downward deflections) with superimposed fast oscillations; for further details, see Sharifullina et al (2005Sharifullina et al ( , 2008. or inhibitory synaptic transmission (Sharifullina et al 2008), and that is preserved despite fluctuations in extracellular Mg 2þ .…”

“…Activation of NMDA receptors is not the only glutamatergic stimulus to induce bursting. In fact, pharmacological stimulation by 3,5-dihydroxyphenylglycine (DHPG) of subtype 1 receptors of group I metabotropic glutamate receptors (mGluR; widely expressed in the brainstem; Del Negro & Chandler 1998) evokes a characteristic pattern of bursting (6.5 + 0.6 Hz) that falls within the range of the so-called theta oscillations (Sharifullina et al 2005; figure 1b). These bursts, which are preceded by a significant rise in cell input resistance and are usually accompanied by fast oscillations (18 + 8 Hz; see rapid transients in figure 1b), are insensitive to NMDA receptor blockers and are due to a large enhancement of AMPA receptor-mediated responses at the network and motoneuron levels .…”

“…250 mm) coronal slice of the neonatal rat brainstem in which the nucleus hypoglossus can be readily identified and single living motoneurons can be viewed with infrared microscopy. In our studies, we have employed whole-cell patch clamp recording from hypoglossal motoneurons together with their histochemical analysis (Sharifullina et al , 2005Lamanauskas & Nistri 2006. Bursts are defined as large, sustained changes in membrane potential (or holding current) caused by periodic up and down swings of the baseline, while oscillations are more rapid, low-amplitude fluctuations.…”