Witzemann / Koenen Group
In order to explain these developmentally regulated changes one has to dissect the individual steps that result finally in synaptic activity, which can be done by experimentally modulating synaptic activity. The acetylcholine receptors, e.g., represent key molecular components that transmit signals from motor nerves to muscle. Specific changes of their structure and function in genetically engineered mouse models will contribute to our understanding of how these receptors can regulate synapse formation.
Furthermore, we also generate animal models carrying mutations that cause neuromuscular disorders such as congenital myasthenia or cardiac diseases in human patients. Our long term goal is to understand inherited muscle dysfunctions, in particular channelopathies and generate mouse models of human diseases that may help to develop therapies fore such diseases.
The neuromuscular junction - a model synapse
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(A) Neuromuscular junctions in diaphragm at birth. The densely packed embryonic-type acetylcholine receptors are evenly distributed across oval shaped endplates, innervated by several nerves. (B) 20 days after birth, endplate architecture has undergone characteristic changes. The receptors are organized in arborized structures, which will be even more pronounced at older age. Endplates are now innervated by a single nerve and embryonic acetylcholine receptores have been replaced by adult-type acetylcholine receptors.
© Witzemann / Koenen
Motor neves (green, stained by anti-neurofilament antibodies) innervate
muscle fibers of diaphragm muscle at synaptic contact sites. The neuromuscular junctions (red, acetylcholine receptors at the
postsynaptic membranes are labeled with fluorescent α-bungarotoxin) show
a high degree of plasticity and adapt to altering physiological needs
during development in a muscle-specific manner.
(A) Neuromuscular junctions in diaphragm at birth. The densely packed embryonic-type acetylcholine receptors are evenly distributed across oval shaped endplates, innervated by several nerves.
(B) 20 days after birth, endplate architecture has undergone characteristic changes. The receptors are organized in arborized structures, which will be even more pronounced at older age. Endplates are now innervated by a single nerve and embryonic acetylcholine receptores have been replaced by adult-type acetylcholine receptors.
