Pervasive synaptic branch removal in the mammalian neuromuscular system at birth.
Using light and serial electron microscopy, we show profound refinements in motor axonal branching and synaptic connectivity before and after birth. Embryonic axons become maximally connected just before birth when they innervate ∼10-fold more muscle fibers than in maturity. In some developing muscles, axons innervate almost every muscle fiber. At birth, each neuromuscular junction is coinnervated by approximately ten highly intermingled axons (versus one in adults). Extensive die off of terminal branches occurs during the first several postnatal days, leading to much sparser arbors that still span the same territory. Despite the extensive pruning, total axoplasm per neuron increases as axons elongate, thicken, and add more synaptic release sites on their remaining targets. Motor axons therefore initially establish weak connections with nearly all available postsynaptic targets but, beginning at birth, massively redistribute synaptic resources, concentrating many more synaptic sites on many fewer muscle fibers. Analogous changes in connectivity may occur in the CNS.
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Juan C
JC
Tapia
John D
JD
Wylie
Narayanan
N
Kasthuri
Kenneth J
KJ
Hayworth
Richard
R
Schalek
Daniel R
DR
Berger
Cristina
C
Guatimosim
H Sebastian
HS
Seung
Jeff W
JW
Lichtman
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D002038:Bungarotoxins / Q000378:metabolism; D002772:Cholera Toxin / Q000378:metabolism; D004622:Embryo, Mammalian; D021621:Imaging, Three-Dimensional; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008954:Models, Biological; D009046:Motor Neurons / Q000502:physiology* / Q000648:ultrastructure; D024510:Muscle Development / Q000502:physiology*; D009469:Neuromuscular Junction / Q000196:embryology / Q000254:growth & development* / Q000648:ultrastructure
D002038:Bungarotoxins; D008164:Luminescent Proteins; D002772:Cholera Toxin