Hypertonia and hyperreflexia are classically described responses to upper motor neuron injury. However, acute hypotonia and areflexia with motor deficit are hallmark findings after many central nervous system insults such as acute stroke and spinal shock. Historic theories to explain these contradictory findings have implicated a number of potential mechanisms mostly relying on the loss of desc...

Using adult male C57BL/6 mice that express a yellow fluorescent protein transgene in their motor neurons, we induced experimental autoimmune encephalomyelitis (EAE) by immunization with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG peptide) in complete Freund's adjuvant (CFA). Control mice of the same transgenic strain received CFA without MOG peptide. Early in the course of their illn...

The inherited motor neuron disease spinal muscular atrophy (SMA) is caused by deficient expression of survival motor neuron (SMN) protein and results in severe muscle weakness. In SMA mice, synaptic dysfunction of both neuromuscular junctions (NMJs) and central sensorimotor synapses precedes motor neuron cell death. To address whether this synaptic dysfunction is due to SMN deficiency in motor ...

Abstract Background Type 1 spinal muscular atrophy is a rare, progressive neuromuscular disease that caused by low levels of functional survival motor neuron (SMN) protein. Risdiplam an or...

Movement is the behavioral output of neuronal activity in the spinal cord. Motor neurons are grouped into motor neuron pools, the functional units innervating individual muscles. Here we establish an anatomical rabies virus-based connectivity assay in early postnatal mice. We employ it to study the connectivity scheme of premotor neurons, the neuronal cohorts monosynaptically connected to motor...

background: als is the most devastating form of motor neuron disease, and the chance of survival is 3 to 5 years after the diagnosis is made. the pathogenesis of the disease is unknown. several upper and lower motor neuron symptoms such as weakness, gait bradykinesia, and muscle atrophy have been reported. the core muscles are considered to be the center of the functional kinetic chain due to t...

The evolutionary origin of novelties is a central problem in biology. At a cellular level this requires, for example, molecularly resolving how brainstem motor neurons change their innervation target from muscle fibers (branchial motor neurons) to neural crest-derived ganglia (visceral motor neurons) or ear-derived hair cells (inner ear and lateral line efferent neurons). Transplantation of var...

Multiple muscle agonists and antagonists acting for all the joint movements in the upper and lower limb exist. This redundancy of motor control is very valuable in normal physiology, but when a central nervous system injury with resulting upper motor neuron syndrome takes place, the source of the functional impairment may be difficult to localize. In this paper we discuss the use of gait and mo...

Cultured ESCs can form different classes of neurons, but whether these neurons can acquire specialized subtype features typical of neurons in vivo remains unclear. We show here that mouse ESCs can be directed to form highly specific motor neuron subtypes in the absence of added factors, through a differentiation program that relies on endogenous Wnts, FGFs, and Hh-mimicking the normal program o...

The therapeutic potential of embryonic stem (ES) cells is promising, but in many cases limited by our inability to promote their differentiation to specific cell types, such as motor neurons. Here we provide the first report of the successful differentiation of human ES cells to cells of a motor neuron phenotype. A renewable source of neuroepithelial cells was generated from human ES cells. Ext...