PNS Structure - Anatomy & Physiology

()Map NERVOUS AND SPECIAL SENSES (Map)

Introduction

• Peripheral Nervous System is made up of: Cranial and Spinal Nerves

• Spinal nerves are named after the vertebra immediately above it, except for cervical vertebra.

• There are 7 cervical vertebrae and 8 cervical spinal nerves.

• The peripheral nervous system can be divided into the somatic nervous system and autonomic nervous system.

• The somatic nervous system co-ordinates body movements and also receives external stimuli. It basically regulates activities that are under conscious control.

• The autonomic nervous system is then split into the sympathetic nervous system, parasympathetic nervous system, and enteric division.

• The sympathetic nervous system is the ‘fight or flight’ system which comes into role when an animal is under threat, it's main neurotransmitter is adrenaline.

• The parasympathetic nervous system is the ‘rest and digest’ system which is responsible for digestion. It’s main neurotransmitter is acetylcholine.

Structure

Peripheral Nerve Structure

• Nerve fibres reside in a connective tissue matrix called the endoneurium and are gathered together into bundles or fascicles defined by a second connective tissue layer called the perineurium.
• Groups of fascicles are then gathered together in a third connective tissue layer called the epineurium.
• Thus, peripheral nerves have a three-tiered hierarchical arrangement of connective tissue.
• Renaut bodies are loose, cigar-shaped whorls of extracellular matrix within fascicles. They are common in horse nerves and may also occur in human and rat peripheral nerves at points of stress or compression.

Nerve Fibre

• The nerve fibre consists of the impulse-carrying axon, which is surrounded by an ensheathing cell, the Schwann cell, which in turn is surrounded by an acellular basal lamina that is continuous along the length of the nerve.
• Nerve fibres come in various discrete diameter groups, which are reflected in their conduction velocities.
• The larger the diameter the more rapid the rate of impulse conduction.
• Particular targets or receptors are associated with axons of a particular diameter, for example:
  • Those connected to muscles spindles have a large diameter (20 um) and conduct at 120 m/s
  • The smallest myelinated fibres are about 1um and conduct at around 6 m/s.
  • The smallest fibres of all are the unmyelinated fibres (the high-threshold sensory afferents, or C-fibres, and post-ganglionic autonomies) and have a diameter of between 1 and 0.1 um. These fibres do not conduct by saltatory conduction and have very slow conduction rates of around 0.5 m/s.

The Axon

• An outer membrane called the axolemma,
• Within this there is the axoplasm which is continuous with the cytoplasm of the neuron.
• There are no ribosomes, either free or attached to endoplasmic reticulum in axons and therefore, no protein synthesis.
• Protein synthesis takes place within the cell body and some dendrites.
  • All protein replacement required for the maintenance of the axon depends on proteins being imported from the cell body.
• A critical feature of the axon is its cytoskeleton, which consists of two key elements:

1. The Neurofilaments
   • Neurofilaments are intermediate filaments of about 10 nm diameter, and belong to the same class as other cytoskeletal proteins such as keratin, desmin, vimentin, or GFAP of astrocytes.
   • Neurofilaments are formed from a triplet of polypeptide subunits of heavy (~ 200 kD), medium (~ 150 kD) and low (~ 60 kD) molecular weights.
   • Typically, these subunits are heavily phosphorylated and are more numerous than microtubules, especially in large diameter axons, having a pivotal role in determining axon diameter.
   • They are formed in the cell body, transported down the axon by axoplasmic transport and degraded in the terminals by Ca²⁺ activated proteases.
   • In other words, there is a constant turnover of neurofllament within the healthy axon.
2. The microtubules
   • Micro tubules within axons are similar to microtubules elsewhere, consisting of polymerised dimers of alpha and beta tubulin arranged as a hollow tube of about 28 nm.
   • They are relatively abundant in smaller diameter axons, and are also synthesised in the cell body.
   • An important component of the cytoskeleton are the microtubule associated proteins or MAP's and the tau protein.
     • These proteins are important in microtubule assembly and stability.
     • Different classes of MAP's occur in the dendrites and the axons, and to some extent account for the different ultrastructural features that distinguish these two types of neuronal process.
     • They form cross links between adjacent microtubules but also connect to neurofilaments and actin microfilaments, implying complex interactions between the various components of the axon skeleton.

The Schwann Cell

• Myelination in the PNS is achieved by the Schwann cell, a derivative of neural crest cells, which bud off from the neuroepithelium at a very early stage of neurogenesis.
• During development, Schwann cells engage many small axons.
• As axonal diameter increases, Schwann cells eventually relate with only a single axon c.f oligodendrocytes.
  • This single axon is enveloped in a trough by the Schwann cell processes that engulf it.
  • As the processes come together, an inner mesaxon is formed.
  • The leading-edge process continues to move over the axon forming a spiral.
• Myelination, an extremely complex molecular process, occurs when the cytoplasm within the process is extruded allowing the internal surfaces of the membrane to come together as the major dense line, the outer membrane apposition constituting the intraperiod line.
• The alternating pattern of these two form the lamellae of compacted myelin.
• The myelin sheath is attached to, and is an integral part of, the Schwann cell on which it is dependent for its maintenance.

• A single Schwann cell forms a single myelin sheath or internode.
• There is a reasonably constant relationship between the myelin thickness and the internodal length, which in turn is associated with axon calibre.
• Large axons have long, thick myelin sheaths, and therefore also conduct more rapidly.
• The internodes do not abut one another but are separated by an exposed area of axon called the node of Ranvier.
• If the axons remain of small diameter, then a Schwann cell will continue to associate with many axons, although none of them are myelinated.
  • Thus, even unmyelinated axons retain a Schwann cell ensheathment.
  • These non-myelinating Schwann cells are sometimes referred to as Remak cells.

Axoplasmic Transport

• Neurons are very large cells and most of a neurons cytoplasm is present in its processes while most of the cells RNA is located in cell body (Nissl substance).
• These cells have therefore evolved mechanisms to transport large macromolecules and organelles up and down processes.

Anterograde Transport

• Two basic forms of anterograde transport can be recognised:

Fast anterograde transport

• Transports all membranous organelles such as synaptic vesicles
• Occurs at a rate of around 400mm/day (recent evidence suggests that there are many form of fast anterograde transport, mediated by different kinesins).
• Fast anterograde transport depends critically on oxidative metabolism, and is, in fact, independent of the cell body.
• The "motor" molecule is an ATPase called kinesin

Slow anterograde transport

• Deals with cytoskeletal elements and large soluble proteins.
• Slow anterograde transport can be further sub-divided into:
  • A slow component, which occurs at about 2mm/day (neurofilament, rubulin, actin)
  • A fast component, which occurs at around 4 mm/day, transporting all other proteins (eg myosin, clathrin).

Retrograde Transport

• Retrograde transport returns materials from the axon terminal to the cell body, either for degradation or restoration and reuse.
• As with fast anterograde transport, particles move along microtubules.
• The motor molecule for retrograde transport is dynein which is a microtubule-associated ATPase.
• The retrograde transport system is important not only for returning material to the cell body, but also provides the means whereby target-derived trophic factors, such as nerve growth factor (NGF) for dorsal root ganglion neurons, are conveyed to the cell body where they promote cell survival.

WikiPath Neurolical Information

Needs to be integrated with above content

The Nerve Fibre

• The nerve fibre consists of the:
  • Axon
    • Carries impulses
  • Schwann cell
    • Ensheaths the axon
  • Basal lamina
    • Surrounds the Schwann cell

The Axon

• The axon consists of:
  • An outer membrane, called the axolemma.
  • The axoplasm.
    • This is contained within the axolemma.
    • Itis continuous with the cytoplasm of the neuron.
  • NO ribosomes (free of attached to the ER).
    • Therefore no protein synthesis can take place in the axon.
    • All protein required for the maintenance of the axon depends on proteins being imported from the cell body.
  • The cytoskeleton.
    • This is a key feature of the axon, which consists of two key elements:
      1. Neurofilaments
         • Neurofilaments are the axon's intermediate filaments.
           • 10 nm diameter.
           • Formed from three polypeptide subunits, which tend to be heavily phosphorylated.
         • Neurofilaments are more numerous than microtubules, especially in large diameter axons.
           • The have a pivotal role in determining axon diameter.
         • Neurofilaments are formed in the cell body, transported down the axon and degraded in the terminals by Ca²⁺ activated proteases.
           • I.e there is a constant turnover of neurofilaments.
      2. Microtubules
         • Axonal microtubules are similar to microtubules elsewhere.
           • 28nm diameter.
           • Consist of polymerised dimers of alpha and beta tubulin arranged as a hollow tube.
         • Relatively abundant in smaller diameter axons.
         • Synthesised in the cell body and transported down the axon.
         • Microtubule associated proteins (MAPs) and the tau protein are important components of the cytoskeleton.
           • These proteins contribute to microtubule assembly and stability. They:
             • Form cross links between adjacent microtubules.
             • Connect microtubules to neurofilaments and actin microfilaments.
               • This implies complex interactions between the components of the axon cytoskeleton exist.
           • The classes of MAPs present differ between the dendrites and the axons.
             • This may account for the different ultrastructural features that distinguish these two types of neuronal process.

Axoplasmic Transport

• Neurons are very large cells.
  • A high proportion of a neurons cytoplasm is present in its processes.
  • However, the cell's protein producing machinery (the Nissl substance) is located in the cell body.
• To overcome these issues, neurons have evolved mechanisms to transport large macromolecules and organelles up and down their processes.

Anterograde Transport

• Anterograde transport moves substances from the cell body to the axon.
• Two forms of anterograde transport are recognised:

1. Fast anterograde transport
   • All membranous organelles are transported by fast anterograde transport.
   • Movement occurs at around 400mm/day.
   • Microtubules act as a static track along which the organelles can move, driven by the ATPase kinesin which acts as a "motor" molecule.
   • Fast anterograde transport depends on oxidative metabolism.
     • However, it is independent of the cell body.
   • Anything which interfering with with energy supply or cytoskeleton necessary for fast anterograde transport has profound effects on the health of the axon.
     • Agents such as colchicine or vincristine block microtubule assembly, disrupting fast anterograde transport.
       • They also block the microtubules of the mitotic spindle, having an antimitotic effect. This makes them useful in anticancer therapy.
2. Slow anterograde transport
   • This transports cytoskeletal elements and large soluble proteins.
   • There are two components so slow anterograde transport
     • A slow component.
       • Transport occurs at around 2mm/day.
       • Neurofilaments, rubulin and actin actin are transported in this manner.
     • A fast component.
       • Movement occurs at around 4 mm/day.
       • All other proteins are transported this way, for example myosin and clathrin.

Retrograde Transport

• Retrograde transport returns materials from the axon terminal to the cell body.
  • The purpose of this is either for degradation or for restoration and reuse.
• Particles move along microtubules, as for fast anterograde transport.
  • Dynein, a microtubule-associated ATPase, is the motor molecule for retrograde transport.
• Apart from returning material to the cell body, target-derived trophic factors are conveyed by retrograde transport to the cell body where they promote cell survival.
  • An example of such a trophic factor is nerve growth factor (NGF), which promotes the growth of dorsal root ganglion neurons.
  • Neurons are particularly dependent on a supply of trophic factors during development.
  • Research is being undertaken into the use of trophic factors to promote cell survival during degenerative pathology.
• The retrograde transport system can be "hijacked" by harmful substances to gain entry to the peripheral neuron and ultimately the CNS. For example:
  • Viruses: herpes simplex virus, rabies.
  • Toxins: tetanus, heavy metals.

The Schwann Cell

• Schwann cells provide myelination in the PNS.
  • They are derived from neural crest cells.
• During development of the nervous system, Schwann cells interact with many small axons.
  • Schwann cells eventually relate to only one axon, as axonal diameter increases with maturation of the system.
    • Oligodendrocytes, that myelinate the CNS, differ from Schwann cells in that they interact with many axons.

The Process of Myelination

1. Initially, the single axon to be myelinated by the Schwann cell sits in a trough formed by the Schwann cell processes.
2. The processes come together to enclose the axon, forming an inner mesaxon.
3. The leading-edge process continues to move over the axon, creating a spiral of Schwann cell around it.
4. Cytoplasm within the proces is extruded, meaning the axon is wrapped in Schwann cell membrane (myelin) alone.
   • The internal surfaces of the membrane, now vacated of cytoplasm, come together as the major dense line.
   • The outer membrane forms the intraperiod line.
5. *The alternating pattern of these major dense line and the intraperiod line form the lamellae of compacted myelin.
6. The myelin sheath remains attached to, and is an integral part of, the Schwann cell.
   • The myelin is therefore dependent on the Schwann cell for its maintenance.

Relationship With Axons

• A single Schwann cell forms a single myelin sheath or internode.
  • One cell does not myelinate the whole length of an axon!
• Myelin thickness is related to internodal length, which in turn is associated with axon calibre:
  • Large axons have long, thick myelin sheaths, and therefore also conduct more rapidly.
• The internodes do not abut one another but are separated by an exposed area of axon called the Node of Ranvier.
  • Action potentials are able to leap between Nodes of Ranvier in saltatory conduction. This increases conduction speed.
• If the axon diameter remains small, then a Schwann cell will continue to associate with many axons, although none of them are fully myelinated.
  • Thus, even unmyelinated axons retain a Schwann cell ensheathment.
  • These non-myelinating Schwann cells are sometimes referred to as Remak cells.

Fibre Types

• Nerve fibres can be assigned to different fibre types depending on their diameter and conduction velocity.
  • The larger the fibre diameter, the more rapid the rate of impulse conduction.
  • Particular targets or receptors are associated with axons of a particular diameter, for example:
    • Those connected to muscles spindles have a large diameter (20 um) and conduct at 120 m/s
    • The smallest myelinated fibres are about 1um and conduct at around 6 m/s.
    • The smallest fibres of all are the unmyelinated fibres.
      • These are the high-threshold sensory afferents, or C-fibres, and post-ganglionic autonomic fibres.
      • They have a diameter of between 1 and 0.1 um.
      • These fibres do not conduct by saltatory conduction and have very slow conduction rates of around 0.5 m/s.

Connective Tissue

• Peripheral nerves have a three-tiered hierarchical arrangement of connective tissue.
  • A nerve fibre is surrounded by a connective tissue matrix called the endoneurium.
  • Bundles, or fasicles of neurons are enclosed in a second connective tissue layer called the perineurium.
  • Groups of fascicles are then gathered together in a third connective tissue layer called the epineurium.
• Renaut bodies may be present in some species.
  • They are loose, cigar-shaped whorls of extracellular matrix within fascicles.
  • Common in horse nerve.
  • May also occur in human and rat nerves at points of stress or compression.

Blood Supply

• The epineurium is penetrated by the vascular supply to the nerve.
  • This blood supply is known as the vasa nervorum.
• Only capillaries occur within the endoneurial compartment.
  • The capillaries of the endoneurium are joined by tight junctions and provide a barrier to large macromolecules.
    • This forms the basis of the blood-nerve barrier (BNB), which has similarities to the blood-brain barrier of the CNS.
      • The BNB appears to be relatively weak in the sensory ganglia because fenestrations occur between endothelial cells in this location.
        • Sensory ganglia are therefore more vulnerable to blood-borne agents.
• A further "barrier" is provided by the perineurium.
  • This consists of sheets of flattened cells, connected by tight junctions, and covered on both sides by a basal lamina.
    • The only route across this structure is trans- rather than inter-cellular.