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

Abstract

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.

Cerebellar cortical output encodes temporal aspects of rhythmic licking movements and is necessary for normal licking frequency

“…Licking, swallowing, suckling and breathing are all vitally important movements controlled by brainstem pattern generators (Nistri et al. , 2006; Barlow, 2009; Cifra et al. , 2009).…”

Postnatal developmental profile of neurons and glia in motor nuclei of the brainstem and spinal cord, and its comparison with organotypic slice cultures

“…Likewise, brainstem hypoglossal motoneurons (HMs) controlling tongue muscles represent an important motor output for CPGs expressing breathing, vocalization, suckling and swallowing (Lowe,1980; Jean,2001), and are early targets for bulbar ALS (DePaul and Abbs,1987; DePaul et al,1988; Haenggeli and Kato,2002; Mitchell and Borasio,2007). Models to mimic the initial dysfunction of these cells prior to the full ALS manifestation have related electrophysiological deficit to cell damage (Nistri et al2006; van Zundert et al,2008; Cifra et al,2009; Nani et al,2010; Cifra et al,2011). Despite the functional role of glia in controlling HM output, for example by regulating glutamate uptake (Nistri et al,2006), little is known about the type of glia at this developmental stage, and its relation to neuronal numbers.…”

Novel mechanism for hyperreflexia and spasticity

“…Gap junction blockers have been reported to depress rhythmogenesis in the respiratory pre-Botzinger complex (Elsen et al , 2008), the retrotrapezoid nucleus (Hewitt et al , 2004), and the nucleus of the tractus solitarius (Parisian et al , 2004). Although few studies on chewing and swallowing have been carried out using gap junction blockers, there is little doubt that gap junctions are present in the trigeminal nucleus (Honma et al , 2004), and hypoglossal (Cifra et al , 2009) neurons are electrically coupled. Jim Lund, in collaboration with Verdier and Kolta, was instrumental in determining that at least some electrical coupling is present in the trigeminal mesencephalic nucleus (Verdier et al , 2004).…”