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Novel mouse model reveals distinct activity-dependent and -independent contributions to synapse development
- Source :
- PLoS ONE, Vol 6, Iss 1, p e16469 (2011), PLoS ONE, PLoS One
- Publication Year :
- 2011
- Publisher :
- Public Library of Science (PLoS), 2011.
-
Abstract
- The balanced action of both pre- and postsynaptic organizers regulates the formation of neuromuscular junctions (NMJ). The precise mechanisms that control the regional specialization of acetylcholine receptor (AChR) aggregation, guide ingrowing axons and contribute to correct synaptic patterning are unknown. Synaptic activity is of central importance and to understand synaptogenesis, it is necessary to distinguish between activity-dependent and activity-independent processes. By engineering a mutated fetal AChR subunit, we used homologous recombination to develop a mouse line that expresses AChR with massively reduced open probability during embryonic development. Through histological and immunochemical methods as well as electrophysiological techniques, we observed that endplate anatomy and distribution are severely aberrant and innervation patterns are completely disrupted. Nonetheless, in the absence of activity AChRs form postsynaptic specializations attracting motor axons and permitting generation of multiple nerve/muscle contacts on individual fibers. This process is not restricted to a specialized central zone of the diaphragm and proceeds throughout embryonic development. Phenotypes can be attributed to separate activity-dependent and -independent pathways. The correct patterning of synaptic connections, prevention of multiple contacts and control of nerve growth require AChR-mediated activity. In contrast, myotube survival and acetylcholine-mediated dispersal of AChRs are maintained even in the absence of AChR-mediated activity. Because mouse models in which acetylcholine is entirely absent do not display similar effects, we conclude that acetylcholine binding to the AChR initiates activity-dependent and activity-independent pathways whereby the AChR modulates formation of the NMJ.
- Subjects :
- Embryology
animal structures
Mouse
Muscle Fibers, Skeletal
Neuromuscular Junction
Neurophysiology
lcsh:Medicine
Biochemistry
Mice
Model Organisms
Developmental Neuroscience
Animals
Receptors, Cholinergic
lcsh:Science
Biology
Motor Neurons
Motor Systems
Receptor Aggregation
lcsh:R
Proteins
Neurochemistry
Animal Models
Neurotransmitters
Molecular Development
musculoskeletal system
Axons
Acetylcholine
Axon Guidance
Phenotype
Acetylcholine Receptors
Models, Animal
Synapses
Mutant Proteins
lcsh:Q
Neurochemicals
Molecular Neuroscience
Research Article
Developmental Biology
Neuroscience
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 6
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.pmid.dedup....8bdb6ce8e28ef4042e5551e76b008f09