Lecture 13 Nerve 2, Oct 04, 2017 (Dr.

Viau)
Chapter 9
3rd edition: pg. 185-218
4th edition: pg. 211-249
IMPORTANT: Cerebellar cortex/cerebellum was not covered in lectures – please read on your own.

Nervous tissue overview

• Ganglion (PNS): Cluster of nerve cell bodies outside the brain and spinal cord (ie. in the PNS)
where many synapses occur (one exception that was not covered in class and you won’t be
examined on are sensory Dorsal Root Ganglia which don’t have synapses).
• Nucleus (CNS): Group, cluster or concentration of nerve cell bodies within the brain and spinal cord
where many synapses occur.
• Autonomic Innervation (involuntary): In the autonomic nervous system there are pre-ganglionic
neurons that originate in the brain or spinal cord and post-ganglionic neurons that originate in the
peripheral ganglia
• ie. Innervating stomach muscles. A pre-ganglionic neuron (primary neuron) originating in
the thoracic spinal cord travels down to the celiac ganglion where it synapses with a post-
ganglionic neuron (secondary neuron) that then goes on to innervate the stomach muscles.

Anatomy of Neurons:
1) Cell body: nucleus, golgi apparatus, RER, mitochondria
2) Axon
- Neurofilaments: plays a structural role, providing a structural backbone for nerve dendrites and
axon extensions
- Microtubules: play a role in transport of cargo, including vesicles with neurotransmitters
- Smooth endoplasmic reticulum: extends from the soma to the axon terminal, occasionally
associated with axonal and vesicular membranes there. The SER conveys the
molecules/building blocks, both lipid and protein-based, for membrane assembly.
3) Axon terminal: synaptic vesicles, mitochondria

Synaptic Transmission:
Know the six steps of synaptic transmission (see page 5 slide 1 of lecture powerpoints) and understand
the subcellular organelles and structures involved in each step
1) Vesicle transport
2) Vesicle loading
3) Depolarization
4) Exocytosis
5) Binding of neurotransmitters
6) Depolarization

Please note: Neuronal (and muscle fiber) depolarization is initiated by an influx of positive sodium ions
(NA+) across the plasma membrane through voltage-gated sodium channels and it is extinguished by the
efflux of potassium ions (K+) across the plasma membrane through voltage-gated potassium channels
(see textbook, pg. 198 3rd Ed, pg. 224 4th Ed, and Fig 9:16A)

Glia:
• Non-neuronal, non-conducting cells that assist in the process of neurotransmission
• Functionally, they provide biochemical (speed up impulses), structural, nutritive (growth and
maintenance), and immune (scavenge toxins, debris) support
 • Glia can help speed up impulses by forming a myelin sheath that wraps around axons and
electrochemically insulates them in sections. There are gaps between each myelin sheath section
called "Nodes of Ranvier". Depolarization events jump from node to node as they move down the
axon with increased velocity compared to a bare, unmyelinated axon (See Fig 9.16B)
• The degree of myelination affects impulse speed; different impulse speeds are important for
different functions (ie. conscious motor impulses need to travel at high velocity and are thus
heavily myelinated compared to unconscious autonomic motor impulses which travel more
slowly and thus are moderately or not myelinated at all)
• Unmyelinated axons have lower impulse speeds because they are leaky (Na+ ions leak out of
axons) and every micron of the axon would need to be individually depolarized in order to
move a signal

Clinical correlation:
1. Multiple Sclerosis (MS):
- Loss of CNS myelin is a primary driver of MS
- MS is an autoimmune disease
2. Amyotrophic lateral sclerosis (ALS):
- A loss of myelin occurs as a secondary manifestation of a primary loss of somatic motor neurons
(this also occurs after acute trauma causing motor nerve injury)

Types of Glia
In the PNS
1. Schwann cells (located in the PNS)
• Myelinated axons:
• Schwann cell wrap many times around one axon to form many layers of Schwann cell plasma
membrane = myelin sheath that insulates the axon plasma membrane underneath the wrapping
• Schwann cells form discontinuous myelin sheaths (ie. forms Nodes of Ranvier).
• Unmyelinated axons:
• A single Schwann cell can "surround" up to 10 axons. These axons are not wrapped or
insulated and continue to communicate with the extracellular space (figure 9-8)

In the CNS
2. Oligodendrocytes (located in the CNS)
• Myelinate neurons in the CNS and serve to increase impulse velocity
• 1 oligodendrocyte can wrap around and myelinate many, many axons
• Functional analog of Schwann cell but can contact multiple nerve axons

3. Protoplasmic and Fibrous Astrocytes (CNS) – “star cells”

• Send out cell process that often contact blood vessels and maintain local blood flow (influence
oxygen and energy consumption)
• Functions to scavenge ions and maintain homeostasis in order to provide nutritive support to
neurons
• Facilitate transport between blood and CNS that can be nutritive for both neurons and glia; therefore
they facilitate/control transport across the blood-brain barrier (BBB) but they are not thought to
form the barrier itself
• Protoplasmic astrocytes occur in grey matter
• Fibrous astrocytes are found in white matter
4. Microglia (CNS)
• Immune scavengers; phagocytic/macrophage-like
• They continually extend and retract their processes and are attracted to damaged neurons by
paracrine factors

5. Ependymal Cells (CNS)

• Form a simple epithelium (most often simple cuboidal) that continuously lines:
a) Surface of the brain beneath the pia mater
b) Inner surface of the brain ventricles
c) Inner surface of the central canal of the spinal cord
• Synthesize, secrete, and excrete cerebrospinal fluid (CSF)
• Tight junctions (zonula occludens) between neighboring ependymal cells prevent CSF from leaking
back into capillaries in (they form the blood-CSF barrier)

Please note: Like neurons, glial cells arise from ectoderm/neuroectoderm (except microglia which arise
from the mesoderm); the originating primary germ layers of the embryo (ectoderm, mesoderm, endoderm)
are discussed in the development lectures; To definitively distinguish between neurons and glial cells,
immunostaining for intermediate filaments is often carried out (neurofilaments in neurons, glial fibrillary
acidic protein (GFAP) in neuroectoderm-derived astrocytes and ependymal cells; vimentin in
mesodermally derived microglia)

Connective tissue coverings or 'investments' of nervous system structures:

All CT coverings in the PNS and the CNS are derived from mesoderm

PNS (coverings surround peripheral nerves which are often mixed motor/sensory)
Understand the spatial relationships and structure of the PNS’ connect tissue coverings
1) Outer epineurium (dense irregular connective tissue; thick and strong)
2) Middle perineurium (dense irregular connective tissue, thin)
3) Innermost endoneurium (loose connective tissue with reticular fibers)

Please note: the nomenclature and the arrangement is very similar to the connective tissue coverings of
skeletal muscles.

CNS (known collectively as the meninges)

Cover the surface of the brain and the spinal cord - located between nervous tissue and the skull and
vertebral bones)
Understand the spatial relationships and structure of the meninges
1) Outer dura mater (dense irregular connective tissue, highly collagenous, type I)
2) Middle arachnoid mater (has spider like projections) (dense irregular connective tissue with some
elastic fibers on its outer aspect and loose connective tissue on its inner aspect that form thin
trabeculae that contact the pia mater)
3) Innermost pia mater (intermediate between dense connective tissue and loose connective tissue).
4) Subarachnoid is the space between the arachnoid mater and the pia mater where small blood
vessels travel to supply and drain both the brain and spinal cord; it is also where cerebral spinal
fluid (CSF) is located outside of the ventricular system

Clinical correlation: Meningitis, which is caused by inflammation of the connective coverings of the brain
and spinal cord; develops in response to infections, drug abuse, cancer, or physical injury. It is curable,
but has devastating effects (ie. dementia, death due to the pressure on CNS structures) if left untreated
Blood Brain Barrier Is Critical For Maintaining Brain Homeostasis via:
1) Capillary endothelium
- Formed by the epithelium that lines the blood vessels of the brain (the simple squamous epithelial
inner lining of capillaries)
- Many tight junctions (referred to as fascia occludentes here) and no pores (or fenestrations) in
capillary endothelial cells prevent free diffusion of macromolecules and ions across the
endothelium
- Not entirely impenetrable, as lipid-soluble substances can pass freely, and macromolecules and
ions can be actively transported across this continuous epithelial endothelium via pinocytosis and
endocytosis/exocytosis
2) Ependymal cells
- Continuous lining of the brain that synthesizes, secretes, and excretes CSF
- Maintains the blood-CSF-brain barrier
3) Pericytes are often present, but probably have more of a stem/repair role than a role in forming a
barrier
4) Neurons and astrocyte endfeet are present but they are involved in control and
movement/absorption of material rather than as part of the functional barrier

Please note: while not directly part of the BBB, the ependymal epithelium (simple cuboidal epithelium)
lines the surface of the brain and spinal chord and the inner lining of spinal canal and the internal
ventricles of the brain

Ventricular system:
• 4 cavities deep within the brain
• Cerebral spinal fluid (CSF) fills the ventricles and helps to act as a liquid cushion to protect the
brain against impact
• CSF also contains nutrients, neurotransmitters, and waste material
• Choroid plexus = Specialized clusters of ependymal cells that surround collections of capillaries
within the ventricles. These structures actively transport ions, glucose, and other solutes from the
capillaries into the central ventricles, which create an osmotic gradient down which water flows
assisted by pinocytosis. This movement from the capillaries into the brain ventricles produces the
CSF
• CSF flows from the ventricles into the continuous central canal of the spinal cord. It also flows out
into the subarachnoid space through small openings at the base of the brain.
• CSF returns to the blood by small protrusions of the arachnoid mater that pierce through the dura
mater (Arachnoid villi) and excretes CSF from the brain via diffusion and one way valves, into the
blood via cranial venous sinuses (large expanded vein-like structures that are located within seams
in the dura mater that ultimately drain into the internal jugular vein; described in more detail in
CAPS 391)

Please note: the brain ventricles and the central canal of the spinal cord are continuous as both are
originally generated from the central lumenal cavity of the neural tube during embryonic development

White Matter vs. Grey Matter (CNS)

• White matter: refers to collection of myelinated axons, and is involved principally in conduction of
information from one location to another within the CNS and spinal cord via tracts
• Grey matter: refers to neuronal cell bodies. This is found in the cortices of the brain and the horns in
the spinal cord. Grey matter principally integrates information at specific locations within the CNS