In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 30, No. 3 ( 2010-01-20), p. 849-857
Abstract:
Low levels of survival motor neuron (SMN) protein result in spinal muscular atrophy (SMA), a severe genetic disease characterized by motor impairment and premature lethality. Although SMN is a ubiquitous protein, motor neurons are much more vulnerable to low levels of SMN than other cells. To gain insight into the pathogenesis of SMA, we have compared synaptic function of motor terminals in wild-type and severe SMA mice at different ages and in two proximal muscles. Our results show that mutant muscle fibers fire normal action potentials and that multi-innervated terminals are functional. By studying the characteristics of the three main components of synaptic transmission in nerve terminals (spontaneous, evoked, and asynchronous release), we found that the kinetics of the postsynaptic potentials are slowed and evoked neurotransmitter release is decreased by ∼55%. In addition, asynchronous release is increased ∼300%, indicating an anomalous augmentation of intraterminal bulk Ca 2+ during repetitive stimulation. Together, these results show that the reduction of SMN affects synaptic maturation, evoked release, and regulation of intraterminal Ca 2+ levels.
Type of Medium:
Online Resource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.4496-09.2010
Language:
English
Publisher:
Society for Neuroscience
Publication Date:
2010
detail.hit.zdb_id:
1475274-8
SSG:
12
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