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Paul Banaszkiewicz Paul Banaszkiewicz Section Editor, Segment Author
Chris Ghazala Christopher George Ghazala Segment Author
  • It is important to have an understanding of the microstructure of a nerve and how this relates to how well a nerve recovers from an injury.
  • The nervous system consists of the central (brain and spinal cord) and peripheral nervous systems.
  • In the adult, the spinal cord extends from the medulla oblongata and terminates at the conus medullaris at the level of the L1 or L2 vertebrae.
  • The brain is divided into the forebrain, midbrain and hindbrain; the forebrain contains the cerebral hemispheres, thalamus and hypothalamus.
  • Surrounding the central nervous system are three meningeal layers: pia mater, arachnoid mater and dura mater. The subarachnoid space contains cerebral spinal fluid.
  • The central nervous system is primarily composed of glial (neuroglia) cells and neurons.
  • The peripheral nervous system is formed by the 12 pairs of cranial nerves and the 31 pairs of spinal nerves from the spinal cord.
  • Measuring up to 45 cm, the spinal cord extends from the medulla oblongata at the foramen magnum to the lower level of L1 or upper border of the L2 vertebrae in the adult, terminating as the conus medullaris.
  • The ligamentum denticulatum stabilises the spinal cord within the spinal canal and extends from the pia mater to the arachnoid and dura maters.
  • On the anterior cord surface lies the deep anterior median fissure and posteriorly runs the median sulcus.
  • A transverse section of the cord demonstrates an area of H-shaped grey matter, consisting of sensory and motor nerve cell bodies; this dense area forms three main projections seen at cross-section: ventral, lateral and dorsal horns. The central canal runs down the centre of the grey matter and communicates with the fourth ventricle.
  • The dorsal horn receives sensory information via the dorsal root; the ventral horn contains the cell bodies of α-motor neurons that form the ventral root and convey motor impulses via action potentials to muscle fibres; the muscle fibre innervated by a single neuron is termed a motor unit.
  • The 31 pairs of spinal nerves (eight cervical; 12 thoracic; five lumbar; five sacral and one coccygeal) arise at the spinal segments.
  • The dorsal root ganglion conveys sensory information; the ventral root ganglion conveys motor impulses.
  • The dorsal and ventral roots join at the intervertebral foramen, exiting as the spinal nerve and immediately dividing into anterior and posterior rami.
  • The peripheral region of a cross-section contains white matter tracts of myelinated sensory and motor axons, which are divided into columns (funiculi) of specialised regions.
  • The dorsal columns contain fibres, which sense fine touch, proprioception and vibration. These ascending columns are formed by the fasciculus gracilis and lateral to this the fasciculus cuneatus.
  • The lateral corticospinal tract transmits impulses associated with fine voluntary motor control. The cell bodies arise in the contralateral cerebral cortex of the frontal and parietal lobes. Axons pass via the internal capsule to the cerebral peduncles and then the majority of fibres decussate in the medulla oblongata and descend as the lateral corticospinal tract in the spinal cord.
  • The lateral spinothalamic tract transmits pain and temperature and crude sensation.
  • A typical neuron consists of a cell body (soma), which contains the nucleus and associated organelles; often this is at the dendritic region of the neuron. Dendrites extend from the surface of the soma and communicate with neighbouring synapses. The major projection of the neuron is the axon, which originates from a thickened projection of the cell body termed the axon hillock.
  • The axon is divided into numerous segments; the initial segment is the first part of the axon that is closest to the axon hillock. The axon ends in a number of presynaptic terminals, with each terminal subdividing into synaptic processes termed terminal boutons or synaptic knobs. These terminal portions contain neurotransmitters, which are stored in synaptic vesicles and are released through exocytosis.
  • Neurons are unipolar if the axon and dendrite emerge from the same region of the soma, bipolar if they emerge from opposite ends of the soma and multipolar if there or two or more dendrites and these are separate to the projecting axon.
  • Many axons are myelinated so that they are insulated and can more effectively transmit their impulses, the action potential. Myelin is a protein-lipid sheath around the axon and in the peripheral nervous system is formed by Schwann cells; whereas in the central nervous system, cells termed oligodendrocytes produce the myelin. Nodes of Ranvier are periodic gaps in the myelin sheath.
  • Neurotransmitters are secreted at the terminal part of the axon, at the synaptic boutons, and protein synthesis associated with these molecules takes place in the cell body. Axonal transport takes place along microtubules, facilitated by dynein and kinesin.

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Figure 1. Motor neuron

  • Action potentials are “all-or-nothing” electrical signals that convey information.
  • Neurons can be stimulated by electrical, chemical and mechanical factors. This results in the generation of non-propagated and propagated potentials (action potentials), and these electrical impulses are the result of ionic changes across the cell membrane (potential difference; measured in millivolts, mV).

Resting membrane potential

  • At rest, the inside of the cell is more negative with respect to the outside, and a resting membrane potential of approximately –70 mV exists.
  • The concentration of K+ions is greater inside the cell, while Na+ions are more concentrated outside the cell; a difference which is regulated by the Na+-K+ATPase pump, which exchanges Naand K+against their concentration gradients.

Depolarisation

  • Various voltage and ligand-gated ion channels are present in the lipid-bilayer membrane and voltage-gated Na+channels can undergo conformational change in response to a specific depolarising stimulus, permitting Na+influx into the cell. A threshold potential (~–55 mV) from the evoking stimulus needs to be reached to initiate the action potential and more of the voltage-gated Na+channels undergo conformational changes to become active. Na+influx exceeds that of other ion channels and the membrane potential becomes positive (+60 mV), reaching the equilibrium potential forNa+. This is a positive feedback and activates further voltage-gated channels.
  • At this potential difference, the Na+channels close and are an inactive closed state; they are refractory to further stimuli while in this phase.
  • Repolarisation of the cell back to the resting state results from the efflux of K+ions out of the cell through voltage-gated K+channels. Compared to voltage-gated Na+channels, K+channels take longer to open and their activity is more sustained, thus producing efflux of K+ions out of the cell. The net result is a negative restingmembrane potential and repolarisation of the cell membrane. Slow closing of these channels to an inactive state leads to hyperpolarisation of the cell and the membrane is in a relative refractory state in which a further action potential can be initiated only if the evoking stimulus exceeds the normal magnitude. The Na+-K+ATPase pump restores the cell to the normal resting potential of –70 mV.
  • Current is generated and there is propagation of the action potential down the axon. The normal membrane resting potential is negative withrespect to the extracellular environment; depolarisation of the cell membrane results in an action potential if the threshold stimulus is reached and the inside of the axon at its peak is more positive with respect to theoutside. This causes current to flow to the neighbouring negative region of the axon and initiate an action potential by activating Na+gated ion channels. The direction of propagation is unidirectional due to the refractory nature of the cell membrane to further depolarisation.

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Figure 2. Membrane potential changes during an action potential, demonstrating the opening and closing of voltage-gated Na+ and K+ ion channels.

  • Neurons communicate at synapses between dendrites and the terminal boutons. Chemical synaptic communication predominates, and when the action potential reaches the terminal bouton, synaptic vesicles fuse with the membrane, releasing their neurotransmitters into the synaptic cleft through the process of exocytosis.
  • Neurotransmitters can be excitatory or inhibitory and can also be classified based on size; small or large-molecule transmitters. Neurotransmitters are synthesised at the terminal bouton and stored in synaptic vesicles.
  • Acetylcholine is the primary neurotransmitter at the neuromuscular junction and it is synthesised from choline and acetyl-CoA, with the enzyme choline acetyltransferase. It is then transported from the cytoplasm into synaptic vesicles by a vesicle-associated transporter.
  • When the action potential reaches and depolarises the presynaptic membrane, voltage-gated Ca2+channels open, causing the influx of Ca2+ into the axon down its electrochemical gradient. Ca2influx causes the synaptic vesicles to fuse with the presynaptic membrane and release, through exocytosis, their neurotransmitter into the synaptic cleft.
  • At the synaptic cleft, acetylcholinesterase metabolises acetylcholine, hydrolysing the neurotransmitter to choline and acetate.

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Figure 3. Release of acetylcholine at the cholinergic synapse.  Acetylcholine is synthesised from acetyl Co-A and choline and transported into synaptic vesicles by VAT.  When the action potential reaches the terminal bouton, voltage-gated Ca2+ channels open and the influx of Ca2+ down its electrochemical gradient causes the vesicle to fuse with the pre-synaptic cell membrane and release its contents through exocytosis. 

CASE BASED DISCUSSIONS

Nerve structure and function

Question :What are the major events that occur  in neuromuscular transmission

  • Motor neuron depolarization causes action potential to travel down the nerve fiber to the NMJ
  • Depolarization of the axon terminal causes an influx of Ca2+ which  triggers fusion of the synaptic vesicles and release of  neurotransmitter (ACh)
  • ACh diffuses across the synaptic cleft and binds to post-synaptic  ACh receptor (AChR) located on the muscle fiber at the motor  end-plate
  • Binding of ACh to AChRs opens the channels causing an influx of  Na, depolarization of the sarcolemma that travels down the t-  tubules and ultimately   causes the release of Ca2+ from the  sarcoplasmic reticulum – this results in contraction.
  • Unbound ACh in synaptic cleft defuses away or is hydrolyzed  (inactivated) by AChE

Question: Can you draw me out a neuromuscular junction?

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Figure 4.Candidate drawing neuromuscular junction

Active Yes
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QUESTION 1 OF 1

Concerning the neuromuscular junction (motor end plate)

QUESTION ID: 1052

1. Botox blocks AC receptors at the motor end plates
2. Malignant hyperthermia is a life threatening clinical syndrome of hypermetabolism involving skeletal muscle due to an allergy
3. Neostigmine is an antidote for non depolarizing blockers
4. Succinylcholine blocks the effect of AC at the neuromuscular junction
5. With Myasthenia gravis the release of AC from the end plate is blocked

Further Reading

  • 1. Griffin JW, Hogan MV, Chhabra BA, Nicole DD. Peripheral nerve repair and reconstruction. JBJS (Am) 2013; 95: 2144–2151.

References

  • 1. Barrett K, Brooks H, Boitano S, Barman S. Ganog’s review of medical physiology, 24th edn. McGraw-Hill Medical, 2012.