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Neuromuscular junctions in the diaphragm muscle of an adult mouse.
Dr. Bruce Patton

[Cover art, Nature Neuroscience, June, 2001.]

Nerve terminals were labeled in vivo by "green fluorescent protein" (GFP, here shown blue), which is expressed in the motor nerves by transgenic methods. The postsynaptic surfaces of the muscle are labeled with rhodaminated alpha-bungarotoxin (shown yellow), a snake venom toxin which binds to (and blocks) muscle acetylcholine receptors. The majority of the muscle, and the glial cells which cover the nerve, are unlabeled (black). A single confocal optical section is shown, reflected about the midline of the image.

Several aspects of synaptic specialization are apparent. Nerve terminals (blue) are branched and varicose, unlike thin pre-terminal axons (not shown). The distribution of terminal varicosities (boutons) is mirrored in the muscle fiber surface by form-fitting postsynaptic indentations in the muscle membrane, which also contain high concentrations of ACh receptors (yellow). Striations visible in the distribution of the ACh receptors mark the location of synaptic folds, deep invaginations which fenestrate postsynaptic surfaces at NMJs in mouse and man (and even snake). In return, "active zones" in the nerve terminal membrane are located precisely opposite to the postsynaptic folds (not shown). Active zones are special molecular complexes that regulate the timing and location of neurotransmitter release by controlling synaptic vesicle fusion. Thus, the machinery for neurotransmitter release and detection are maintained in exquisite registration. Several laminin isoforms appear to collaborate in promoting these features of coincident pre- and postsynaptic differentiation.

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