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Give an example of a wiring process mediated by an activity-dependent competitive mechanism.

Apr 7, 2016


Activity-dependent competitive mechanisms abound in the nervous system. Of special interest is the development of the connection between motor neurons and the skeletal muscles, which relies on an activity-dependent competition with particularly high stakes: life or death for the neurons!

Two Cells Enter, One Cell Leaves

In addition to constructing a miniature model of the world inside your skull for you to inhabit, the brain is also tasked with generating sequences of actions in the real world.

The brain's primary effectors are the skeletal muscles, more commonly known as the muscles. When you feel the desire to take a step forward, reach for an object, or scratch an itch, the motor cortex must determine how to tug on these big bundles of springs in order to swing the bones to which they are attached in precisely the correct fashion to produce the desired movement.

These commands rely on a well-made interface between the nervous system and the muscles. Each muscle fiber needs to be matched to exactly one neuron, and all of the motor neurons need to be matched to at least one muscle fiber.

To complicate matters further, the neurons in question are born inside the spinal cord, induced to adopt their fate by a variety of morphogens, while the muscle cells are born far away, in a totally different germ layer, and, in one final twist of complexity, assemble themselves, Voltron-style into a single, more powerful muscle fiber.

So how are we to ensure that our motor neurons and our muscle fibers are well matched?

One modest proposal is to generate far more neurons than you need, and any that don't manage to find a motor neuron can just be killed. In order to ensure that this diktat is followed, nature adopts a strategy straight out of Saw II: motor neurons are, from the moment they are born, searching frantically for the antidote to a poison that will kill them when a timer runs out. They are, like Biggie Smalls, born ready to die. The antidote is released by muscle fibers, but it is only released in small quantities and to synaptically-connected neurons that drive activity in the muscle.

So, the motor neurons rush out from the ventral horn of the spinal cord, making a mad dash for the nearest muscle fiber, guided by the various axon guidance factors. Some cells find a partner and begin to form synapses, also called neuromuscular junctions, but others are not so lucky. These unlucky cells are drawn to the spurts of antidote that diffuse away from these immature synapses in a desperate attempt to survive, and then they are locked in a duel to the death with the original tenant – whoever can make a stronger synapse faster will choke the other one out.

Only about half of the motor neurons born in the ventral horn will survive to become functional.