Elimination by shedding

Synapse elimination occurs via a combination of axon retraction and the shedding of vesicles dubbed “axosomes,” according to Derron Bishop, Thomas Misgeld, Jeff Lichtman (Harvard University, Cambridge, MA), and colleagues. The axosomes appear to end up inside glia, and may help carry both signals and essential functional materials to this supporting cell type.

Terrestrial vertebrates need synapse elimination because their nervous systems are not dedicated, hard-wired circuits but redundant. Overconnection in uncoordinated neonates gradually gives way, via synapse elimination, to single, point-to-point neural connections and fine motor control.

Lichtman's group got a new look at the process at the mouse neuromuscular junction by correlating light and serial electron microscopy (EM). The resolution of the EM allowed them to show that axosomes were derived from but distinct from axon tips. Axosome formation may be cell autonomous, but glia may also help. Axon remnants were deformed as if they were being pinched off by another cell, and axosomes ended up inside the ensheathing Schwann cells.

Lichtman and colleagues hope to confirm glial involvement using mice with fluorescent markers in both their glia and neural organelles. Any transfer from axon to glia may serve two functions. The axosomes contain synaptic vesicles and the cytoplasmic constituents for delivering them; this machinery may help glia to release small amounts of neurotransmitter and thus maintain the temporary viability of deinnervated muscles. Second, the axosomes may carry a signal to tell the glia that, with the axon gone, the glia are no longer needed and would be better off dead.

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