Learn More
Spinal muscular atrophy (SMA) is a major genetic cause of death in childhood characterized by marked muscle weakness. To investigate mechanisms underlying motor impairment in SMA, we examined the spinal and neuromuscular circuitry governing hindlimb ambulatory behavior in SMA model mice (SMNΔ7). In the neuromuscular circuitry, we found that nearly all(More)
Recent studies suggest that glial cells actively participate in the formation, function, maintenance, and repair of the chemical synapse. However, the molecular mechanisms of glia-synapse interactions are largely unknown. We have shown previously that Schwann cell-conditioned medium (SC-CM) promotes synaptogenesis in Xenopus nerve-muscle cocultures. The(More)
Emerging evidence suggests that the neurotransmitter acetylcholine (ACh) negatively regulates the development of the neuromuscular junction, but it is not clear if ACh exerts its effects exclusively through muscle ACh receptors (AChRs). Here, we used genetic methods to remove AChRs selectively from muscle. Similar to the effects of blocking ACh(More)
Spinal muscular atrophy (SMA), a motoneuron disease caused by a deficiency of the survival of motor neuron (SMN) protein, is characterized by motoneuron loss and muscle weakness. It remains unclear whether widespread loss of neuromuscular junctions (NMJs) is involved in SMA pathogenesis. We undertook a systematic examination of NMJ innervation patterns in(More)
Recent studies suggest that progressive motoneuron death in amyotrophic lateral sclerosis (ALS) is non-cell autonomous and may involve the participation of non-neuronal cells such as glial cells and skeletal muscle. Therefore, a drug that targets motoneurons as well as neighboring non-neuronal cells might be a potential therapeutic strategy to delay disease(More)
Glial cells are widely distributed throughout the nervous system, including at the chemical synapse. However, our knowledge of the role of glial cells at the synapse is rudimentary. Recent studies using a model synapse, the vertebrate neuromuscular junction (NMJ), have demonstrated that perisynaptic Schwann cells (PSCs), which are the glia juxtaposed to the(More)
Emerging studies demonstrate that perisynaptic Schwann cells (PSCs), which are the glia cells juxtaposed to the motor nerve terminal, actively participate in multiple aspects of the neuromuscular junction. During development, PSCs guide and promote synaptic growth. In adult muscles, PSCs can sense nerve stimulation by increasing intracellular calcium and(More)
In this study we examined the developmental roles of acetylcholine (ACh) by establishing and analyzing mice lacking choline acetyltransferase (ChAT), the biosynthetic enzyme for ACh. As predicted, ChAT-deficient embryos lack both spontaneous and nerve-evoked postsynaptic potentials in muscle and die at birth. In mutant embryos, abnormally increased nerve(More)
To investigate the in vivo role of glial cells in synaptic function, maintenance, and development, we have developed an approach to selectively ablate perisynaptic Schwann cells (PSCs), the glial cells at the neuromuscular junction (NMJ), en masse from live frog muscles. In adults, following acute PSC ablation, synaptic structure and function were not(More)