Axoplasmic Transport

Synaptic membrane proteins including ion channels and receptors, cytoskeletal protein structures which expel neurotransmitter vesicles, organelles including mitochondria, and enzymes required for the synthesis and metabolism of transmitters are manufactured only in the cell bodies of neurons where biochemical machinery exists for protein synthesis and assembly (Golgi apparatus and ribosomes). These materials or their precursors are then moved through the axon (or dendrite) to the nerve terminal by a cytoskeletal mechanism similar to a conveyer belt or bucket brigade. Time lapse photography of neurons in cell culture show mitochondria (large organelles which produce chemical energy in the form of ATP) floating down axons like barges on a river. Recent technology such as video enhanced contrast microscopy (Allen, 1987) has shown vesicles zipping along microtubules on the surfaces of axoplasm extruded from squid neurons. Transmitters are synthesized throughout the entire neuron as the enzymes which catalyze transmitter formation move along the cytoskeletal apparatus from cell body to terminal. The highest enzymatic activity and transmitter concentrations are reached in the terminal boutons. Thus the plasticity of a synapse, its efficacy, readiness and threshold which appear to regulate learning and memory in neural nets over time all depend on axoplasmic transport.

Several separate and independent axoplasmic transport processes have been identified by following the movement of various tracers. The fastest move at a rate of 400 millimeters per day (about 500 nanometers per second), the slowest barely one millimeter per day. The mechanical parts of the system are microtubules and contractile proteins attached to specific sites on microtubule walls. These contractile proteins (dynein or kinesin) utilize chemical energy in the form of ATP hydrolysis to contract in orchestrated sequences of bucket brigade activity. What is not understood is the mechanism by which microtubules orchestrate the cooperative sequential activities of the attached contractile proteins. The main stream of axoplasmic transport can be stopped by drugs such as colchicine, which depolymerizes microtubules. Axoplasmic transport generally flows from the cell body toward the tips of fibers. In motor nerves, axoplasmic transport flows in the same direction as the impulse traffic; in primary sensory neurons it flows in the opposite direction to the sensory impulses. In dendrites, the main flow is also from the cell body to the periphery. These are all examples of anterograde axoplasmic flow. There is also simultaneous transport in the opposite direction toward the cell body called retrograde axoplasmic flow which apparently brings feedback information to the cell machinery to regulate the production of transmitter enzymes and other materials. It might also return worn or broken down cell constituents to be recycled. These trophic feedback mechanisms create dynamic neurons capable of changing shape and function as an adaptation to ongoing experience without excessive loss of old information. Synapses, dendritic spines, dendritic branch patterns and membrane proteins are continually changing, yet the memories they contain are somehow maintained by the ever present and ever-changing cytoskeleton.

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