Anatomy and Structure of Axons - Axons are the primary transmission lines of the nervous system - Axons can extend up to one meter or more - Diameter of axons is variable, ranging from microscopic to up to 20µm - Axons in the central nervous system typically show multiple telodendria - Two types of axons: myelinated and unmyelinated - Myelin is a fatty insulating substance formed by Schwann cells and oligodendrocytes - Myelinated axons have gaps in the myelin sheath known as nodes of Ranvier - Myelination enables rapid electrical impulse propagation called saltatory conduction - Myelinated axons form the white matter in the brain - Bundles of myelinated axons make up nerve tracts in the central nervous system

Axonal Region and Synaptic Connections - The axonal region includes the axon hillock, initial segment, rest of the axon, telodendria, and terminals - Proteins needed for axon growth and waste removal are transported through the axoplasm - Axon hillock is the area formed from the cell body of the neuron as it extends to become the axon - Axonal initial segment is a structurally and functionally separate microdomain of the axon - Axon initial segment helps initiate action potentials and supports neuron cell polarity - Axons make contact with other cells at synapses - Synapses can be along the length of an axon (en passant synapses) or at the ends of axonal branches - Axon terminals join dendrites or cell bodies of other neurons - Special molecular structures transmit electrical or electrochemical signals across synapses - A single axon can target multiple parts of the brain and generate thousands of synaptic terminals

Clinical Significance - Axon dysfunction can cause neurological disorders affecting peripheral and central neurons - Nerve fibers are classified into group A, group B, and group C fibers - In sensory neurons, axons are called afferent nerve fibers - Some species have axons that consist of several regions functioning independently - The corpus callosum, formed of axons, is the largest white matter tract in the human brain - Neurapraxia, axonotmesis, and neurotmesis are degrees of severity for peripheral nerve injury - Concussion is a mild form of diffuse axonal injury - Axonal injury can cause central chromatolysis and is a major cause of inherited and acquired neurological disorders - Crushed axons undergo Wallerian degeneration, where the part furthest from the cell body degenerates - Dying back of an axon, known as Wallerian-like degeneration, can occur in neurodegenerative diseases

Axonal Transport - Microtubules form in the axoplasm at the axon hillock - Microtubules are arranged along the length of the axon, in overlapping sections, all pointing towards the axon terminals - The overlapping arrangement provides routes for the transport of different materials from the cell body - Numerous vesicles of all sizes can be seen moving along the microtubules and neurofilaments in both directions between the axon and its terminals and the cell body - Outgoing anterograde transport carries mitochondria and membrane proteins needed for growth to the axon terminal, while ingoing retrograde transport carries cell waste materials from the axon terminal to the cell body

Development and Growth - The axon is one of the six major stages in the overall development of the nervous system - Neurons initially produce multiple neurites, but only one becomes the axon - Axon specification may precede axon elongation - Cutting an underdeveloped axon can change polarity and allow other neurites to become the axon - External force can cause a neurite to elongate and become an axon - Proteins, neurotrophic factors, and extracellular matrix play a role in axonal development - Netrin is a secreted protein involved in axon formation - Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NTF3) are involved in axon development - Increased activity of PI3K at the tip of the axon promotes axonal development - Disrupting PI3K activity inhibits axonal development - The neurite with the lowest actin filament content becomes the axon - PGMS concentration and f-actin content are inversely correlated - Growing axons move through their environment via the growth cone - The growth cone has a lamellipodium and filopodia for exploration - Cell adhesion molecules (CAMs) and extracellular matrix provide a sticky substrate for axonal growth - Guidepost cells assist in the guidance of neuronal axon growth