Motoneuron death can occur over several spinal levels with disease or trauma, resulting in muscle denervation. We tested whether cotransplantation of embryonic neurons with 1 or more neurotrophic factors into peripheral nerve improved axon regeneration, muscle fiber area, reinnervation, and function to a greater degree than cell transplantation alone. Sciatic nerves of adult Fischer rats were c...

Notch signaling plays a well-described role in regulating the formation of neurons from proliferative neural precursors in vertebrates but whether, as in flies, it also specifies sibling cells for different neuronal fates is not known. Ventral spinal cord precursors called pMN cells produce mostly motoneurons and oligodendrocytes, but recent lineage-marking experiments reveal that they also mak...

Recent molecular genetic studies suggest that the expression of transcription factors in the developing spinal cord helps determine the morphological and physiological properties of neurons. Using the zebrafish preparation, we have examined the properties of neurons marked by alx, a zebrafish homolog of mammalian Chx10. We performed morphological and physiological studies using transgenic zebra...

The influence of motoneuron pool properties on the stability of the stretch reflex at the ankle in subjects with spinal cord injury was tested using a comprehensive model of the reflex pathway. This model included the passive and active components of the triceps surae muscles, muscle spindles, neural transport delays, limb mechanical properties, and a lumped parameter model of the motoneuron po...

BACKGROUND Amyotrophic Lateral Sclerosis (ALS) is neurodegenerative disease characterized by muscle weakness and atrophy due to progressive motoneuron loss. The death of motoneuron is preceded by the failure of neuromuscular junctions (NMJs) and axonal retraction. Thus, to develop an effective ALS therapy you must simultaneously preserve motoneuron somas, motor axons and NMJs. A conditioning le...

The brain stem provides most of the noradrenaline (NA) present in the spinal cord, which functions to both increase spinal motoneuron excitability and inhibit sensory afferent transmission to motoneurons (excitatory postsynaptic potentials; EPSPs). NA increases motoneuron excitability by facilitating calcium-mediated persistent inward currents (Ca PICs) that are crucial for sustained motoneuron...

Amyotrophic lateral sclerosis (ALS) is a fatal paralytic disorder caused by dysfunction and degeneration of motor neurons. Multiple disease-causing mutations, including in the genes for SOD1 and TDP-43, have been identified in ALS. Astrocytes expressing mutant SOD1 are strongly implicated in the pathogenesis of ALS: we have shown that media conditioned by astrocytes carrying mutant SOD1(G93A) c...

A single spinal motoneuron receives tens of thousands of synapses. The neurotransmitters released by many of these synapses act on iontotropic receptors and alter the driving potential of neighboring synapses. This interaction introduces an intrinsic nonlinearity in motoneuron input-output properties where the response to two simultaneous inputs is less than the linear sum of the responses to e...

Motoneurons often fire repetitively and for long periods. In sustained voluntary contractions the excitability of motoneurons declines. We provide the first detailed description of the time course of human motoneuron recovery after sustained activity at a constant discharge rate. We recorded the discharge of single motor units (MUs, n = 30) with intramuscular wire electrodes inserted in triceps...