The Neuromuscular System (Part 3) – Neurons and Neuroglia

Following on from our journey through basic brain and spinal cord anatomy, as well as the corticospinal tracts, it is crucial to understand the make-up of these structures and how they all play a role in electrochemical communication to skeletal muscle.

The brain accounts for approximately 2% of an individual’s body mass yet contains up to a trillion neuronal and glial cells. While neurons are the most commonly recognized cell in the nervous system, they are actually outnumbered by approximately 10:1 in terms of glial cells (Figure 1).

Figure 1. Example of number glial cells in relation to nerve cells.

What are glial cells (neuroglia)?

These cells do not form synapses and have a number of crucial roles such as the development of myelin (for neurons within the CNS), early neuronal develoment, extracellular K+ maintenance and reuptake of neurotransmitters after it’s use within neurons (to be covered in more detail in Part 4). Let us begin with the two types of glial cells:

1. Macroglia – Primarily refers to astrocytes and oligodendrocytes. Under some circumstances, these cells may be able to regenerate. In the peripheral nervous system, this would also include Schwann cells.
2. Microglia – Immune cells (macrophages) of the CNS. These cells migrate to sites of injury to remove cellular debris.

Let us briefly discuss the role of each macroglia:

Astrocytes: Found within gray matter and around neurons, blood vessels, and the exterior surface of the brain and spinal cord. Of it’s many roles, it can be thought of as a parent or caretaker cell that is responsible for:

• Structural support and directing the projections/migration of developing neurons.
• Aid with synaptic transmission through astrocytic processes participating in the reuptake of used up neurotransmitters.
• Maintenance of extracellular K+ within the brain and spinal cord, therefore membrane potential. Astrocytes are highly permeable to K+ ions.
• Maintence of the blood brain barrier through astrocytic end feet wrapping around cappillary endothelium and aiding in the tight formation of junctions that do not allow pathogens and lipid soluble solutes into the extracellular fluid of the CNS (Figure 2). (We will definitely cover the above 2 bullet points at a later date!)
• Proliferation of larger astrocytes to aid in repair of damaged neural tissue. These astrocytes are more unique due to size and containing an astrocyte specific protein known as glial fibrillary acidic protein (GFAP).

Figure 2. Various astrocytic functions; encasing capillary endothelium and supporting structure of neuron,

Oligodendrocytes: Mostly found in white matter as they are resposible for forming the lipid-rich myelin around CNS neurons and providing nutrients to the neurons they are wrapped around. These fat layers increase insulation of the axon, thereby increasing the speed of electrical transmission (aka nerve conduction velocity). A single oligodendrocyte may wrap around as many as 40-50 axons (Figure 3).

Schwann cells: These are the PNS equivalent of oligodendrocytes, however each cell can only myelinate a single axon. This may potentially explain why the recovery or remyelination of peripheral nerves may occur at a faster pace.

Figure 3. Myelin of axons within the CNS (made by oligodendrocytes) but by Schwann cells within the PNS.

Neurons (Nerve cells)

Neurons (otherwise known as nerve cells) are specialized cells for the communication of signals to and from other cells. These signals or transmitted information are encoded as electrical and chemical processes (to be covered later) that within fractions of a millisecond. Generally speaking, based on primary function, neurons are of 3 main types (Figure 4):

1. Motor (efferent) neurons – Responsible for motor functions; muscular contraction or gland secretion. (From brain and downwards). The largest of the neurons.
2. Sensory (afferent) neurons – Convey sensory stimuli from the skin, mucous membranes and deeper structures. (To brain and upwards).
3. Interneurons (relay neurons) – Local messengers within the CNS which communicate neural information over short distances (e.g. cell to cell), hence shorter processes and axons.

Figure 4. The three primary types of neurons within the nervous system.

Neurons also vary in complexity, shape, size, length, speed of electrical tranmission and secondary function. Some of this will be further understood as we expand on the structures of a typical neuron. Most neurons will have a cell body (soma or perikaryon) with surrounding branch like structures named dendrites or dendritic zones. Cell bodies will extend into a single axon and end at another cell or dendrite; this region is called the snypatic terminal.

Figure 5. Schematic drawing of a Nissl-stained motor neuron. Representation of the differences between a motor neuron within the CNS and PNS,

Let’s explore the key structures of a neuron:

Cell body: This generally takes up a very small portion of the neuron’s total volume but arising from it are processes by the name of dendrites. The soma and dendrites represent the receptive end of a neuron and tend to be covered the end of other neurons (synaptic terminal) synapsing onto them. Cell bodies contain Nissl bodies made of rough endoplasmic reticulum, which allow for the creation and secretion of proteins crucial for transmission of nerve impulses.

Dendrites: Most neurons have these in large amounts to recieve synaptic information and therefore tends to be larger than the cell body itself. Dendrites are long and thin, thereby isolating and picking up electrical events from another synapse. Dendrite branching may vary based on how the neuron integrates synaptic input. Some dendrites extend into further branches to recieve further synaptic information; these are known as dendritic branches.

Axons: A single axon generally extends from the cell body of a single neuron and is simply a cylindrical tube covered by a membrane (axolemma) and contains a cytoskeleton consisting of neurofilaments and microtubules. These microtubules provide the tunnel like pathway for fast transportation of neurotransmitters alongside the aid of kinesin molecules. In larger neurons, the beginning of the axon can be identified as the cone shaped axon hillock which is the inital segment of the axolemma. This segment is morphologically distinct as it possesses a higher amount of sodium channels, therefore acting as a trigger zone and the initiation of action potentials to travel along the axon and arrive at the terminal. Axons can vary in length as much as from a few microns to over a meter in length.

Myelinated neurons are axons covered in myelin; a sheath of multiple layers of lipid-rich membrane either produced by oligodendrocytes (in the CNS) or Schwann cells (PNS) (Figure 6). The distinct gaps are generally formed in ~1mm increments leaving an opening of the axon where it is exposed to the extracellular fluid pool. These gaps are the nodes of Ranvier. Smaller axons may be unmyelinated (Figure 7), thereby have less insulation and a decreased speed of impulse conduction.

Figure 6. Electron micrograph – cross section of a myelinated nerve in the PNS. The Schwann cell wraps around the axon to envelop it in a myelin sheath that functions as an electrical insulator. Source (http://medcell.med.yale.edu/systems_cell_biology)

Figure 7. Schwann cells and oligodendrocytes can also associate with axons but not wrap them in myelin sheaths. This EM image shows a Schwann cell associated with several small axons but without myelinating the axons. Source (http://medcell.med.yale.edu/systems_cell_biology)

Interesting facts: While axonal transport is generally thought of as cell body –> axon –> terminals (anterograde transport), it can also be terminal –> cell body (retrograde transport). Also, biomechanical injuries (i.e concussion) can lead to axons being torn or sheared which results in a chromatolysis phase. Unfortunately, CNS axonal damage does not recover so quickly and can lead to/become part of major injuries such as diffuse axonal injury (DAI).

Synapses: Neuronal communication occurs where the end of an axon (pre-synaptic terminal) reaches and conveys information to the receptive segment of a receiving cell or neuron (post synaptic). This meeting is known as the synapse or synaptic junctions (in the case of a muscle membrane, it is known as a neuromuscular junction). The majority of synapses in the mammalian CNS are chemical synapses whereby small bubbles (synaptic vesicles) carry a small amount or ‘quanta’ of neurotransmitters across the presynaptic membrane via calcium influx and phosphorylation (to be covered in Part 4 or 5) (Figure 8). Synaptic transmission is not in the form of one axon terminal synapsing with another; it is actually in the form multiple presynaptic terminals converging upon a single cell body. Larger cell bodies can acommodate up to several thousand synaptic terminals.

Figure 8. Synaptic terminal with neurotransmitter substance travelling across to the post synaptic membrane.

Interesting fact: Axons that terminate at another dendrite are termed axodendritic and tend to be excitatory neurons, while axons that terminate at the soma are axosomatic and tend to be inhibitory. Some axons also synapse onto other axons (axoaxonic).

Types of neurons

As mentioned previously, there are 3 main types based on primary function but you will come across a lot more over the course of your studies! Let’s try cover some of these:

Upper motor neurons – found within the cerebral cortex extending to the spinal cord.

Lower motor neurons – found within the spinal cord extending towards the muscle fibers they are responsible for innervating. Lower motor neurons fall into 2 categories:

• Alpha motor neurons – These are large anterior horn neurons that innervate extrafusal fibres within skeletal muscle, which are responsible for overall muscle contraction.
• Gamma motor neurons – These are smaller neurons also found in the ventral horn but innervate the intrafusal fibers within skeletal muscle (where muscle spindles are located). These are not gross detectable movements as these fibres are smaller; 25-30% of the ventral root fibers are made of gamma motor neurons.

 

Types of nerve fibers based on diameter, conduction velocities and physiological characteristics

A fibers are larger, myelinated, have rapid conduction capacity and contain motor/sensory impulses. B fibers are smaller myelinated axons with lower conduction velocities than A fibers and serve autonomic function. C fibers are the smallest and serve autonomic function as well as pain conduction. Sensory fibers are sometimes also classifed numerically (Figure 9).

Figure 9. Nerve fiber types based on alphabetical and numerical (sensory) classification. Modified from Ganong WF: Review of Medical Physiology.

 

Types of Nerve fibers on a physioanatomic basis

Fiber types may also based on a physioanatomic/functional basis:

• Somatic efferent fibres – Motor fibres innervating skeletal muscle. Originate in ventral gray horn and form the ventral root of spinal nerve.

• Somatic afferent fibres – Sensory fibres communicating information from the skin, joints and muscles to the CNS. Form the dorsal root ganglion. Example: afferent fibres within intrafusal fibres are known as Ia and II afferent fibers which feedback information via the dorsal root ganglion regarding muscle length and rate of change. Type Ia afferent fibres monosynaptically communicate with alpha motor neurons to excite (and shorten) the agonist muscle. This is known as the stretch reflex. In addition 1a afferents can lead to alpha motor neurons inhibiting antagonist muscle groups via inhibitory interneurons. Other inhibitory interneurons (Renshaw cells) stop excitatory transmission of the alpha motor neuron to avoid over activity of the agonist muscle (Figure 10). This is called reciprocal inhibition.

Figure 10. Stretch reflex demonstrated the integration of Ia, Ib, II fibres, alpha motor and inhibitory interneurons.

• Visceral efferent fibres – These are the autonomic fibres split into sympathetic and parasympathetic fibres.
• Visceral afferent fibres – Cell bodies located in the dorsal root ganglia and communicate sensory information from the viscera.

That concludes my summary of neurons and neuroglia for today! Stay tuned for the following articles/topics within the NM System series:

• Neurotransmission & Membrane Potentials: Excitatory or Inhibitory?
• Motor Units – Recruitment & Synchronization.
• NM Contraction (Skeletal Muscle anatomy & Sliding Filament theory).

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