Motoneuron firing in amyotrophic lateral sclerosis (ALS)

Abstract

Amyotrophic lateral sclerosis is an inexorably progressive neurodegenerative disorder involving the classical motor system and the frontal effector brain, causing muscular weakness and atrophy, with variable upper motor neuron signs and often an associated fronto-temporal dementia. The physiological disturbance consequent on the motor system degeneration is beginning to be well understood. In this review we describe aspects of the motor cortical, neuronal, and lower motor neuron dysfunction. We show how studies of the changes in the pattern of motor unit firing help delineate the underlying pathophysiological disturbance as the disease progresses. Such studies are beginning to illuminate the underlying disordered pathophysiological processes in the disease, and are important in designing new approaches to therapy and especially for clinical trials.

New perspectives on amyotrophic lateral sclerosis: the role of glial cells at the neuromuscular junction

“…However, it is very important to highlight that, besides MN and NMJ properties, strong evidence indicates that alterations are also present at several other levels of the motor circuit in ALS (reviewed in de Carvalho et al . ).…”

“…This could provide insight into how the relationship of MN excitability and NMJ synaptic dysfunctions relates to the vulnerability of the lower motor circuit in ALS. However, it is very important to highlight that, besides MN and NMJ properties, strong evidence indicates that alterations are also present at several other levels of the motor circuit in ALS (reviewed in de Carvalho et al 2014).…”

Muscular cramp: causes and management

“…by vibratory excitation of 1a afferents, is sufficient to increase the RMP beyond threshold by causing a reduced net outward current flow insufficient to maintain the normal RMP. A brief excitation can then cause rhythmic, repeated firing . Baldissera et al .…”

“…by vibratory excitation of 1a afferents, is sufficient to increase the RMP beyond threshold by causing a reduced net outward current flow insufficient to maintain the normal RMP. A brief excitation can then cause rhythmic, repeated firing [30]. Baldissera et al [28,32] suggested that cramp could be arrested by the combined effect of afferent activity in group Ia and II activity and of pain fibre activation, leading to blockade of the H reflex response pathway and silencing of the continuous motoneuronal discharge (Fig.…”

Formation and characterisation of neuromuscular junctions between hiPSC derived motoneurons and myotubes

“…Muscle wasting and weakness in motoneuron diseases arise predominantly from the loss of motoneurons. Hence, research has focused on investigating the mechanisms of motoneuron cell death (de Carvalho et al, 2014). In addition, there is growing evidence indicating that alterations of NMJs and/or the skeletal muscle itself affect the pathogenic process in amyotrophic lateral sclerosis (ALS) (Miller et al, 2006;Murray et al, 2010;Wong and Martin, 2010).…”