Overview of Peripheral Nervous System

Question 1

What is a neuronal nucleus?

Answer 1

A group of functionally related nerve cell bodies in the CNS (NOT the nucleus of a single cell!)
e.g. inferior olivary nucleus, nucleus ambiguus, caudate nucleus

Question 2

What is a column in the spinal cord?

Answer 2

A group of functionally related nerve cell bodies that form a longitudinal column extending through part or all of the length of the spinal cord.
e.g. Clarke’s column

Question 3

What is a tract or fasciculus (fasciculi)?

Answer 3

A bundle of parallel axons in the CNS (fasciculus is Latin for “bundle”)
e.g. optic tract, corticospinal tract, medial longitudinal fasciculus, fasciculus gracilis

Question 4

What is a ganglion (ganglia)?

Answer 4

A group of nerve cell bodies located in a peripheral nerve or root; its forms a visible lump
e.g. dorsal root ganglia, trigeminal ganglion

Question 5

What is a nerve ramus (rami) or nerve root?

Answer 5

A bundle of axons or nerve fibres. A typical peripheral nerve may have many thousands of individual nerve fibres of many different diameters.

Question 6

What is the structure of sensory (afferent neurons)? What is special about the cell bodies in the dorsal root ganglia?

Answer 6

• Sensory (afferent) neurons have two sets of dendrites-like processes: one in the periphery and one in the spinal cord. To avoid confusion (as axons have previously been defined as carrying AP away from cell body), sensory ‘axons’ in the limbs and body are usually known as sensory nerve fibres.
• Note: there are no synapses on sensory cell bodies in dorsal root ganglia
  (see lecture notes for image)

Question 7

Where do sensory neurons enter the spinal cord? How are spinal nerves formed? How do motor neurons exit the spinal cord? What happens if dorsal roots are severed?

Answer 7

• Sensory neurons enter the spinal cord in the dorsal root. They have their cell bodies outside the spinal cord in the dorsal root ganglion
• Spinal nerves are formed from the fusion of dorsal and ventral roots.
• Motor (efferent) neurons exit in the ventral root. They have their cell bodies in gray matter in the ventral spinal cord.
• If the dorsal roots are severed between the dorsal root ganglion and the spinal cord, the sensory axons cannot regenerate into the spinal cord. This is a major contributing factor to spinal paralysis, as sensory input (via reflexes and otherwise) is a major factor in voluntary movement.

Question 8

Why are we interested in dermatomes? What does loss of sensation in a dermatome indicate? How can this be caused?

Answer 8

• The shapes of dermatomes are discussed in Dr. Vicketon’s lecture: Why are we interested in dermatomes? Because analysis of the area of loss of sensation after a nerve injury can tell us if the injury is in the spinal or peripheral nerve.
• If the zone of loss of sensation is a dermatome the injury is probably in the spinal nerve or dorsal root ganglion in the intervertebral foramen. This could be due to compression due to a fracture or a slipped disk. If the loss does NOT correspond to a dermatome the damage is in the peripheral nerve. Also if a single dorsal root ganglion is infected with shingles the blisters and itching occurs in a single dermatome

Question 9

What is the cauda equina made up of and why? Where can lumbar puncture be carried out?

Answer 9

• The cauda equina is made up of the long lumbar and sacral dorsal and ventral roots, as the adult spinal cord is shorter than the vertebral column, but the roots have to exit in the correct foramina.
• Sampling of cerebrospinal fluid is done by a lumbar puncture at L3 or L4. The spinal cord stops at L1 or L2, so the sampling needle cannot damage it (nerves get pushed out of the way)

Question 10

What do most sensory fibres and motor axons have wrapped around them? What happens where these coverings meet? How can this affect conduction of action potentials?

Answer 10

• Most sensory fibres & motor axons have a sheath of fatty insulation called myelin wrapped around them.
• Myelin is produced by connective tissue cells called Schwann Cells.
• Where two sheaths meet there is a small gap in the myelin called a Node of Ranvier. Action potentials can only occur at these nodes.
• Reducing the number of action potential sites per metre along the nerve fibre increases the speed of conduction of the action potential along the nerve.
• Demyelinating diseases of peripheral nerves damage the myelin sheath and slow down or block conduction of action potentials

Question 11

How is myelin formed? What is is its function? How far apart are nodes in myelinated axons?

Answer 11

• Myelin is formed by the Schwann cell wrapping itself many times around the axon, gradually squeezing out the cytoplasm until multiple layers of cell membranes are left.
• The multiple layers of lipid membrane provide an electrically insulating layer around the nerve fibre so that current flow in and out of the nerve fibre can only occur at the nodes of Ranvier.
• This means action potentials ‘jump’ from one node to the next.
• Nodes are about 5-10mm apart in large myelinated axons

Question 12

What covers individual sensory or motor fibres? How are fibres collected together?

Answer 12

• Individual sensory or motor nerve fibres are surrounded by a thin protective membrane the endoneurium.
• Groups of functionally related nerve fibres are collected together into nerve fascicles; each fascicle is surrounded by perineurium.
• A whole peripheral nerve consists of several fascicles bundled together with blood vessels and all surrounded by epineurium (the epineurial sheath).

Question 13

What features allows nerves to stretch without breaking fibres?

Answer 13

• Nerve fibres are slightly longer than epineurium so nerve can stretch a small amount without breaking fibres

Question 14

What is at the end of the peripheral branches of the sensory nerve fibre in the skin? What are the two types of sensory receptors? What does its type determine?

Answer 14

• The peripheral branches of the sensory nerve fibre end in the skin or muscle as sensory receptors.
• Sensory receptors are either ‘free nerve endings’ where the sensory nerve branches profusely and ends up lying in the extracellular space between tissue cells, or ‘encapsulated nerve endings’ where the nerve ending is surrounded by a specialised connective tissue ‘capsule’.
• The capsule determines the kind of stimulus the nerve ending will be sensitive to.
• E.g. slow pressure, vibration, stretch.

Question 15

What are examples of encapsulated nerve endings?

Answer 15

• Encapsulated nerve endings in skin include Pacinian corpuscles, Meissner corpuscles, Merkels disks and Ruffini corpuscles.

Question 16

What are nerve ending capsules made of? How do they develop in the foetus? How does it become encapsulated?

Answer 16

• Nerve ending capsules are made of connective tissue. When the nerve fibre first grows into the tissue in the fetus it is bare and unencapsulated. Cytokines released from the bare end of the nerve fibre stimulate local connective tissue cells to multiply and form a capsule around it as specified by the particular cytokines from that nerve ending.

Question 17

What do capsules act as? What are examples of this?

Answer 17

• Capsules are a form of mechanical filter. For example, the capsule of a Pacinian corpuscle makes the nerve ending selectively sensitive to high frequency (>50 Hz) vibration. On the other hand the capsule of a Ruffini ending makes the nerve fibre sensitive to pressure on the skin.

Question 18

How do sensory endings trigger action potentials? What is this depolarisation called?

Answer 18

• Sensory nerve fibre endings have special sodium channels in their terminal membrane which open when the axon is bent. When the channel is open it allows sodium ions to enter the terminal which then becomes depolarised. The depolarisation is graded , not all or none. not an action potential; it is called a receptor potential. The receptor potential then triggers an action potential further proximally in the nerve fibre.

Question 19

How are nociceptors formed?

Answer 19

Nociceptors are formed from axons with bare nerve endings in the skin

Question 20

What does distortion of the membrane cause?

Answer 20

Distortion of membrane opens special sodium channels in terminal membrane

Question 21

What does the graded receptor potential trigger and where? What does pressure on the skin do to the axon, and what does this cause? What effevt does stronger pressure have?

Answer 21

• The graded receptor potential triggers action potentials more proximally in in the nerve fibre, normally at the first node of Ranvier in myelinated fibres.
• Weak pressure on the skin bends the axon slightly and produces a small receptor potential which triggers action potentials at a low rate during the pressure.
• Stronger pressure increases the frequency of action potentials; it takes less time to start each action potential. The maximum frequency is limited by the refractory period of the axon.
• As an approximation, the intensity of a cutaneous stimulus is coded by the frequency of the action potentials in its sensory axon

Question 22

How does the nerve fibre respond to different forms of mechanical stimulation? What how do different types of receptors react differently?

Answer 22

• The capsule ‘tunes’ the terminal nerve fibre to respond to different forms of mechanical stimulation. Some receptors only respond transiently to a stimulus and are called rapidly adapting (e.g. Pacinian): others respond for longer and are slowly adapting (e.g. Ruffini). Rapidly adapting receptors only respond at the beginning of a stimulus: they ‘fatigue’ after a second or so to a sustained steady stimulus. Slowly adapting receptors will continue firing to a sustained stimulus but at a gradually reducing rate.
• Rapidly adapting receptors: Pacinian corpuscles, Meissner’s corpuscles.
• Slowly adapting receptors: Ruffini endings, Merkel’s disks

Question 23

Which receptors have a small/large receptive field size? Which are fast/slow?

Answer 23

Meissner’s corpuscle = small and fast
Pacinian corpuscle = large and fast
Merkel’s disk = small and slow
Ruffini’s ending = large and slow

Question 24

What are free nerve endings and what do they respond to? What are they normally called and what is their function? Where are they found?

Answer 24

• Free nerve endings are slowly adapting receptors that form a very fine nerve plexus in the dermis and many other tissues. These free nerve endings respond to chemical stimuli (eg changes in pH, or chemicals like peptides in the extracellular space) in addition to mechanical displacement. These free endings are often called polymodal nociceptors. They detect (local) tissue damage. They normally (not always) produce the sensation of local pain.
• Nociceptor nerve endings are found in all tissues of the body. They respond to tissue damage, but do not signal very accurately the precise location of the damage. This is why pain inside the body may be poorly localised.

Question 25

How are receptors for noxious stimuli formed?

Answer 25

Receptors for noxious stimuli are formed from axons with bare (‘free’) nerve endings.
These fine axons branch profusely in the tissue and form a fine matrix in all organs of the body.

Question 26

Where are the majority of encapsulated sensory receptors located? What happens in hairy skin?

Answer 26

• The majority of encapsulated sensory receptors are in skin or muscle. Hairy skin has few encapsulated endings but contains rapidly adapting peritracheal or hair follicle receptors, a hybrid form between free and encapsulated endings.
• The peritricheal fibers wrap around the base of the follicle and extend up the shaft; bending the hair generates a generator potential in the fibre.

Question 27

How do ‘arrector pili’ muscles cause/react to stimuli?

Answer 27

• Small ‘arrector pili’ muscles anchor hair follicles by attaching the shaft of the hair follicle to the dermal tissue. Upon stimulation, the contracting muscles cause piloerection with the formation of cutis anseri, or goose bumps.
• Erect hairs are more sensitive to deflection so may detect light touch stimuli

Question 28

What differs between different kinds of sensory and nerve endings?

Answer 28

• Different kinds of sensory and motor endings are connected to different diameter nerve fibres that conduct action potentials at different velocities

Question 29

How do you calculate the conduction velocity for myelinated fibres?

Answer 29

Velocity = 6 x diameter in micrometers

Question 30

What are examples of fast and slow pain?

Answer 30

Fast pain = pin prick, burn, etc.

Slow pain = muscle aches, etc.

Question 31

What is a receptive field? What is it used for based on its size?

Answer 31

• A sensory nerve fibre branches when it reaches the skin and supplies a small set of the same receptors in a localised region of skin.. The area of skin innervated by a single nerve fibre is its receptive field (RF).
• Receptive fields on glabrous skin used for tactile discrimation (like the palmar surface of fingers or the outer parts of our lips) have a small size. This improves our ability to localise stimuli.
• Receptive fields are larger on skin regions not used for tactile discrimination like our proximal limbs, back and abdomen.

Question 32

How do receptive fields allow stimuli to be localised?

Answer 32

• Receptive fields of individual nerve fibres overlap. The brain localises a stimulus by processing the information from many fibres simultaneously. Damage to a single fibre does not leave any region of skin anaesthetic. Progressive loss of nerve fibres (as in diabetic neuropathy) leads to a progressive worsening in ability to localise stimuli as there is less and less overlap.

Question 33

What are the signs of peripheral nerve injury?

Answer 33

• Skin areas of analgesia, anaesthesia or paraesthesia
• Muscle weakness or paralysis
• Muscle atrophy
• Skin changes (thinning)
• Hyporeflexia or areflexia
• Possibly neuropathic pain

Question 34

How do nerves repair themselves after injury?

Answer 34

• When a peripheral nerve is cut, the distal part is disconnected from its cell body and degenerates. The Schwann cells around this distal part unwrap themselves from the dead fragments and divide to form a continuous line of cells lining the distal endoneurial sheaths.
• The proximal cut ends of the nerve fibres form growth cones and start to grow back down inside the sheaths guided by chemical factors (cell adhesion molecules or ‘CAM’s) on the inner surface of the Schwann cells

Question 35

What do microtubules do in nerve repair? What is the role of actin filaments? How do these together allow for nerve repair?

Answer 35

• Microtubules in the regrowing axon transport growth-related materials down to the growth cone. At the edge of the cone there are actin filaments which extend out in filopodia. The tips of the filopodia attach (adhere) to the surrounding tissue and then the actin contracts to pull the cone along towards the denervated region. The growth cone filopodia adhere to the cell adhesion molecules on inner surface of the Schwann cells, contract, and pull themselves forward along the tunnel formed by the distal endoneurial sheath and Schwann cells

Question 36

What do the Schwann cells do behind the growth cone? What are the nerve fibres like to begin with? How fast do nerve fibres regenerate? What increases the chance of successful regeneration?

Answer 36

• Behind the growth cone Schwann cells proliferate and start to wrap myelin around the nerve fibre. The nerve fibres are initially very thin and slow conducting. With time they enlarge but may never reach their original diameter. Nerve fibres regenerate at about 1.5 mm/day. Some however never regenerate. The further distal a nerve injury, the more likely there is to be successful regeneration. Nerves may take months or even years to fully recover.

Question 37

What are the four steps of nerve regeneration at the site of injury?

Answer 37

1. Fragmentation of axon and myelin occurs in distal stump
2. Schwann cells form cord, grow into cut, and unite stumps. Macrophages engulf degenerated axon and myelin.
3. Axon sends buds into network of Schwann cells and then starts growing along cord of Schwann cells.
4. Axon continues to grow into distal stump and is enfolded by Schwann cells.