Histology, Axon

In 1860, the German anatomist Otto Friedrich Karl Deiters (1834-1863) described the basic structure of the nerve cell and identified two different protoplasmatic protrusions of the cell body that he termed as "axis cylinder," and "protoplasmatic processes," respectively axons and dendrites (see Illustration of Axon). Axons are the elongated portion of the neuron located in the center of the cell between the soma and axon terminals. In size, the axon may represent over 95% of the total volume of the neuron. Functionally, it carries electrical impulses and projects to synapses with dendrites or cell bodies of other neurons or with non-neuronal targets such as muscle fibers. Concerning length, the length of axons varies according to the function of the neuron. Considering the functional distinction between projection neurons and interneurons, cortical projection neurons (CPNs), also termed as pyramidal neurons and spinal cord projection neurons (dorsal horn neurons), usually have long axons (from several mm and up to 1 m). In contrast, interneurons, that work within local circuits, have a short axonal terminal (up to several mm). The longest axons of the human body are those that make up the sciatic nerve where the length can exceed one meter. Furthermore, compared to projecting neurons, interneurons usually have smaller soma, fewer organelles, and a reduced amount of cytoplasm (axoplasm). Histological observation of axon shows a cylindrical structure, but recent 3D electron microscopy studies demonstrated that probably axon has not the shape of a perfect cylinder. The diameter is variable as it ranges between 1 and 25 micrometers. In squid, it reaches a diameter of 1 mm. The variation of the diameter has important functional implications since the speed of propagation of the impulse (i.e., action potential), besides being dependent on the presence of the myelin sheath, is directly proportional to the diameter of the axon. Moreover, they have demonstrated significant changes in the diameter along the single axon. The axon is one of two types of protoplasmic protrusions of the neuronal soma. The other protrusion is the dendrites. Axons are distinguished from dendrites by several characteristics including: . Dendrites are usually thin while axons typically maintain a constant radius. . Dendrites are limited to a small region around the cell body while axons can be much longer. . Substantial structural differences exist between dendrites and axons. For example, only dendrites contain rough endoplasmic reticulum and ribosomes, and the structure of the cytoskeleton is different. Differences also affect the membrane as it contains mostly voltage-gated ion channels in axons, whereas ligand-gated ion channels are present, especially in dendrites. . Dendrites usually receive signals, while axons typically transmit them. However, all these rules have exceptions. Furthermore, axons generate and transmit all-or-none action potential, whereas dendrites produce depolarizing (below the threshold of the action potential) or hyperpolarizing (lowering the resting membrane potential) graded potentials. Of note, although each neuron has only one axon, bifurcations that are branches of the main axon can be present. A collateral branch is an axonal protrusion over10 micrometers in length. These collaterals provide modulation and regulation of the cell firing pattern and represent a feedback system for the neuronal activity. The terminal part of the axon and collaterals tapers progressively. These parts are called telodendron and continue with the synapse (synaptic knob or button) which represents the specialized structure that comes into contact with another neuron (soma, axon or dendrite), or muscle fiber. Axon extension and growth of new telodendrons (and synapses) are guided by several factors, including the nerve growth factor (NGF). The branching processes, in turn, play a role of fundamental importance in neuroplasticity, for instance, in cognitive processes such as memory and learning. Anatomically and based on the appearance of the protoplasmatic protrusions, neurons are classified into three groups: They are the most common neurons; Shape: a single axon and many dendrites extending from the cell body. Localization: central nervous system (CNS).  Shape: a single short process that extends from the cell body and then splits into two branches in opposite directions; one branch travels to the peripheral nervous system (PNS) for the sensory reception, and the other to the CNS (central process). These neurons have no dendrites as the branched axon serving both functions. Localization: dorsal root ganglion and sensory ganglia of cranes nerves, and some mesencephalic nucleus.  Shape: one axon and one dendrite that extend from the cell body in opposite directions. Localization: retinal cells and olfactory system. Two notable features distinguish the axon from the soma (also referred to as perikaryon). First, no rough endoplasmic reticulum extends into the axon; secondly, the composition of the axonic membrane (axolemma) is fundamentally different from that of the somatic membrane. These structural differences translate into functional distinctions. In fact, since the absence of ribosomes does not allow protein synthesis, all axon proteins originate in the soma. Furthermore, the particular structure of the membrane due to the presence of specific protein channels allows information to travel along the course of the axon. Again, depending on the location within the body, these structures can be covered in sheaths of an insulating material known as myelin. Based on the presence or absence of the myelin sheath, axons are distinguishable into myelinated and non-myelinated axons.  Myelin forms by the concentric wraps of the plasma membrane of neuroglia cells around the axon. These cells are the Schwann cells (or neurolemmocytes) in the PNS and oligodendrocytes in the CNS. As a general rule, oligodendrocytes myelinate multiple adjacent axons, while Schwann cells myelinate only one axon. In structural terms, the myelin sheath wraps the axons discontinuously as it is interrupted at regular intervals called Ranvier nodes (also termed as myelin sheath gaps), which represent the space between two consecutive Schwann cells and at which the axon is devoid of the sheath. In this way, employing the jump mechanism from one Ranvier node to the next, the propagation of the electrical signal is much faster than in the myelin sheathed axons. The cell membrane of Schwann cells is arranged around the axon, forming a double membrane structure (mesaxon), which elongates and wraps itself in a spiral, in concentric layers, around the axon itself. During this winding process, the cytoplasm of the Schwann cell is pushed towards the outside, while the surfaces of the contact membranes end up condensing, forming the lamellae of the myelin sheath. When the myelin sheath wraps around the axon, the mesaxon disappears by fusion of the cytoplasmic membranes in contact, except in correspondence with the innermost gyrus (internal mesaxon) and the outermost gyrus (external mesaxon or neurilemma) where there is a turn outermost rich in the cytoplasm. When the myelin sheath forms by oligodendrocytes (in PNS), the outermost gyrus reduces to a tongue and, in turn, although there is the internal mesaxon, the external one is not recognizable. Functionally, myelin represents an electrical insulator, allowing an increased speed of conduction along with an axon. It facilitates electrical transmission via saltatory conduction. Structurally, myelin is composed of approximately 80% of lipids (mostly cholesterol and variable amounts of cerebrosides and phospholipids) and 20% of proteins. However, depending on its location, myelin has a different composition as CNS myelin has more glycolipid and less phospholipid than PNS myelin.