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THE NERVOUS
SYSTEM: NEURAL
TISSUE
Nervous system functions
•
1. sensory function
– sensory receptors detect internal and external stimuli
– information is sent to CNS via sensory (afferent) neurons within sensory nerves
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2. integrative function
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integrates = processing of information within the CNS
stores info and also makes decisions once info is processed
one important integrative function = perception
processed by interneurons within the CNS
90% of the neurons within the CNS are interneurons
3. motor function
– decision usually manifests itself as a motor command – contraction of a muscle,
secretion by a gland
– motor commands travel along motor (efferent) neurons within motor nerves
– commands are sent to effectors = muscles and glands
Nervous system includes all neural
tissue in body
• about 3% of the total body weight
• Central Nervous System
– Brain and spinal cord (brain = 100
billion neurons, SC = 100 million
neurons)
• Peripheral Nervous System
– All neural tissue outside CNS
– includes the spinal and cranial nerves
A schematic of the vertebrate nervous
system
Figure 21-6
Cells in Nervous Tissue
• Neurons
• Neuroglia
Neuroglia (Glia)
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“glue”
about half the volume of cells in the CNS
smaller than neurons
5 to 50 times more numerous
do NOT generate electrical impulses
divide by mitosis
– however, mature glial astrocytes may not be able to divide – only precursors to
glial populations
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regulate the clearance of neurotransmitters
participate in neural development
– provide growth factors and chemical cues for the development of neurons and their
axonal processes
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Two types in the PNS
– Schwann cells
– satellite cells
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Four types in the CNS
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Astrocytes
Oligodendrocytes
Microglia
Ependymal cells
Astrocytes
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Largest of glial cells
Most numerous
Star shaped with many processes
projecting from the cell body
-two types: protoplasmic, fibrous
-protoplasmic – short branches, found in gray matter
-fibrous – many long unbranched processes, found
in white matter
-processes make contact with the capillaries supplying the
CNS, the neurons of the CNS and the pia mater membrane
covering the brain and spinal cord
•
Help form and maintain blood-brain barrier
– processes wrap around the blood capillaries and isolate the
neuron from the blood supply
-also secrete substances that maintain a unique permeability
for the endothelial cells that line these capillaries – restricts
movement of substances out of the blood
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Provide structural support for neurons
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microfilaments within cytoskeleton
Maintain the appropriate chemical
environment for generation of nerve impulses/action potentials
Regulate nutrient concentrations for neuron survival
Regulate ion concentrations - generation of action potentials by neurons
Take up excess neurotransmitters – take up excess GABA and glutamate
Assist in neuronal migration during brain development
Perform repairs to stabilize tissue – scar formation???
Oligodendrocytes
• fewer processes than astrocytes
• round or oval cell body
• Each forms myelin sheath
around the axons of
neurons in CNS
• Analogous to Schwann
cells of PNS
• Form a supportive
network around CNS
neurons
Microglia
• few processes
• derived from mesodermal cells
that also give rise to monocytes
and macrophages
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Small cells found near blood vessels
15% of the glial cells of the CNS
Phagocytic role - clear away dead cells
– derived from hematopoietic stem cells
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protect CNS from disease through phagocytosis of microbes
migrate to areas of injury where they clear away debris of
injured cells - may also kill healthy cells
Ependymal Cells
• epithelial cells arranged in a
single layer
• range in shape from cuboidal
to columnar
• Form epithelial membrane lining cerebral cavities (ventricles) & central canal
- that contain CSF
• Produce & circulate the cerebrospinal fluid (CSF) found in these chambers
• CSF = colourless liquid that protects the brain and SC against
chemical & physical injuries, carries oxygen, glucose and other necessary
chemicals from the blood to neurons and neuroglia
PNS: Satellite Cells
• Flat cells surrounding PNS axons
• Support neurons in the PNS
• help regulate the chemical environment surrounding the neurons
PNS: Schwann Cells
• each cell surrounds multiple unmyelinated PNS axons with a single
layer of its plasma membrane
• Each cell produces part of the myelin sheath surrounding an axon in
the PNS
• contributes regeneration of PNS axons
Neurons
•what is the main defining characteristic of neurons?
•have the property of electrical excitability - ability to produce
action potentials or impulses in response to stimuli
Representative Neuron
http://www.horton.ednet.ns.c
a/staff/selig/Activities/nervou
s/na1.htm
1. cell body or soma (or perikaryon)
-single nucleus with prominent nucleolus (high
synthetic activity)
-Nissl bodies
-rough ER & free ribosomes for protein
synthesis
-proteins then replace neuronal cellular
components for growth and repair of damaged
axons in the PNS
-neurofilaments or neurofibrils give
cell shape and support - bundles of
intermediate filaments
-microtubules move material inside
cell
-lipofuscin pigment clumps (harmless
aging) - yellowish brown
-the processes that emerge from the
body of the neuron = nerve fibers
-two kinds: dendrites & axons
Neurons
2. Cell processes =
dendrites (little trees)
- the receiving or input
portion of the neuron
-short, tapering and
highly branched
-surfaces specialized
for contact with other
neurons
-cytoplasm contains
Nissl bodies &
mitochondria
3. Cell processes = axons
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Conduct impulses away from cell bodypropagates nerve impulses to another neuron
Long, thin cylindrical process of cell
contains mitochondria, microtubules &
neurofibrils - NO ER/NO protein synth.
joins the soma at a cone-shaped elevation =
axon hillock
first part of the axon = initial segment
most impulses arise at the junction of the
axon hillock and initial segment = trigger
zone
cytoplasm = axoplasm
plasma membrane = axolemma
Side branches = collaterals arise from the
axon
axon and collaterals end in fine processes
called axon terminals
Swollen tips called synaptic end bulbs
contain vesicles filled with neurotransmitters
Axonal Transport
• Cell body is location for most protein synthesis
– neurotransmitters & repair proteins
• however the axon or axon terminals require proteins
– e.g. neurotransmitters
• Axonal transport system moves substances
– slow axonal flow
• movement of axoplasm in one direction only -- away from cell body
• movement at 1-5 mm per day
• replenishes axoplasm in regenerating or maturing neurons
– fast axonal flow
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moves organelles & materials along surface of microtubules
at 200-400 mm per day
transports material in either direction
for use in the terminals or for recycling in cell body
Axonal Transport & Disease
• fast axonal transport route by which toxins or pathogens reach
neuron cell bodies
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tetanus (Clostridium tetani bacteria) – toxin = tetanospasmin
disrupts motor neurons causing painful muscle spasms
“lockjaw” – muscle stiffness usually involves jaw and neck first
interferes with the release of neurotransmitters that result in inhibition
of muscle contraction
– neuronal targets are peripheral motor end plates, CNS, sympathetic NS
– lethal dose = 2.5 ng per kg body weight (e.g. 70 ng for 175 lbs)
• bacteria enter the body through a laceration or puncture injury
– more serious if wound is in head or neck because of shorter transit
time to the brain
Structural Classification of Neurons
• Based on number of processes found on cell body
– multipolar = several dendrites & one axon
• most common cell type in the brain and SC
– bipolar neurons = one main dendrite & one axon
• found in retina, inner ear & olfactory
– unipolar neurons = one process only, sensory only (touch, stretch)
• develops from a bipolar neuron in the embryo - axon and dendrite fuse and
then branch into 2 branches near the soma - both have the structure of axons
(propagate APs) - the axon that projects toward the periphery = dendrites
Structural Classification of Neurons
• Named for histologist that first described them or
their appearance
•Purkinje = cerebellum
•Renshaw = spinal cord
• others are named for shapes
e.g. pyramidal cells
Functional Classification of Neurons
• Sensory (afferent) neurons
– transport sensory information from skin, muscles,
joints, sense organs & viscera to CNS
• Motor (efferent) neurons
– send motor nerve impulses to muscles & glands
• Interneurons (association/integrative) neurons
– connect sensory to motor neurons
– 90% of neurons in the body
The Nerve Impulse
Terms to know
• membrane potential = electrical voltage difference measured across the
membrane of a cell
• resting membrane potential = membrane potential of a neuron
measured when it is unstimulated
– results from the build-up of negative ions in the cytosol along the inside of
the neuron’s PM
– the outside of the PM becomes more positive
– this difference in charge can be measured as potential energy – measured
in millivolts
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polarization
depolarization
repolarization
hyperpolarization
Ion
Channels
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ion channels in the PM of neurons and muscles contributes
to their excitability
when open - ions move down their concentration gradients
channels possess gates to open and close them
two types: gated and non-gated
1. Leakage (non-gated) or Resting channels: are always open, contribute to the resting potential
-nerve cells have more K+ than Na+ leakage channels
-as a result, membrane permeability to K+ is higher
-K+ leaks out of cell - inside becomes more negative
-K+ is then pumped back in
2. Gated channels: open and close in response to a stimulus
A. voltage-gated: open in response to change in voltage - participate in the AP
B. ligand-gated: open & close in response to particular chemical stimuli (hormone,
neurotransmitter, ion)
C. mechanically-gated: open with mechanical stimulation
The resting potential, generated mainly by
open “resting”, non-gated K+ channels
-the number of K+ channels
dramatically outnumbers that
of Na+
-however, there are a few Na
leak channels along the axonal
membrane
AXON
ECF
Graded potentials
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local changes in membrane potential that occur in varying intensities (grades)
– caused by the opening of ion channels in a region of the axonal membrane
• usually ligand-gated or mechanically-gated channels
– typically gated ion channels for sodium – results in a slight depolarization = graded
potential
– region that is being depolarized = active area
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stronger the triggering event = stronger the graded potential that results
– the stronger the trigger the more ion channels open, the greater the depolarization
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spread by passive current flow
– because a local area has begun to depolarize – charge of this area changes
– specifically the inside area gets more positive in relation to the surrounding areas
that are at rest
– the outer area becomes more negative in relation to the surrounding areas that are at
rest
– this produces a current that starts to spread to the surrounding areas – depolarizing
them
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BUT they die over short distances
– this current decreases as it travels further from the originating area
Action Potential
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Resting membrane potential is 70mV
triggered when the membrane
potential reaches a threshold
usually -55 MV
if the graded potential change
exceeds that of threshold – Action
Potential
Depolarization is the change from 70mV to +30 mV
Repolarization is the reversal from
+30 mV back to -70 mV)
• action potential = nerve impulse
• takes place in two stages: depolarizing phase (more positive) and repolarizing
phase (more negative - back toward resting potential)
• followed by a hyperpolarizing phase or refractory period in which no new AP
http://www.blackwellpublish
can be generated
ing.com/matthews/channel.
html
depolarization (increase in MP) results
from opening of Na+ channels. This
opens an increasing number of
voltage-gated Na channels which
depolarizes the membrane more. Once
threshold is reached, a large # of
voltage-gated Na+ channels open and
a rapid increase in MP results
outflow of K+ restores the resting
MP. Na+ channels begin to open
and K+ channels close. K+ outflow
results in hyperpolarization (below
resting) results in a refractory
period.
at a certain stage of depolarization, theMP also
opens voltage-gated K+ channels which permit
the outflow of K+ . The Na+ close and
the MP becomes more negative returning toward
resting MP
Local Anesthetics
• Prevent opening of voltage-gated Na+
channels
• Nerve impulses cannot pass the
anesthetized region
• Novocaine and lidocaine – blocks nerve
impulses along nerves that detect pain
Continuous versus Saltatory Conduction
• Continuous conduction
(unmyelinated fibers)
– An action potential spreads
(propagates) over the surface of
the axolemma
http://highered.mcgrawhill.com/sites/0072437316/student_view0/chapter45/animations.html#
Saltatory Conduction
• Saltatory conduction
-depolarization only at nodes of
Ranvier - areas along the axon
that are unmyelinated and
where there is a high density of
voltage-gated ion channels
-current carried by ions flows
through extracellular fluid from
node to node
http://www.blackwellpublishing.com/matthews/actionp.html
Rate of Impulse Conduction
• Properties of axon
• Presence or absence of myelin sheath
• Diameter of axon
• The propagation speed of a nerve impulse is not related
to stimulus strength.
– Larger = faster conduction
– Myelin 5-7 X faster
– larger, myelinated fibers conduct impulses faster due to size &
saltatory conduction
Myelination increases the velocity of
impulse conduction
Figure 21-15
Action Potentials in Nerve and Muscle
• Entire muscle cell membrane versus only the
axon of the neuron is involved
• Resting membrane potential
– nerve is -70mV
– skeletal & cardiac muscle is closer to -90mV
• Duration
– nerve impulse is 1/2 to 2 msec
– muscle action potential lasts 1-5 msec for skeletal &
10-300msec for cardiac & smooth
• Fastest nerve conduction velocity is 18 times
faster than velocity over skeletal muscle fiber
Synaptic Communication
Synapse
• Synapse
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– Site of intercellular communication
between 2 neurons or between a neuron
and an effector (e.g. muscle)
Permits communication between neurons and
other cells
– Initiating neuron = presynaptic neuron
– Receiving neuron = postsynaptic neuron
Most are axodendritic axon -> dendrite
Some are axoaxonic – axon > axon
• axon terminal swell to form synaptic end bulbs or form swollen
bumps called varicosities
• release of neurotransmitters from synaptic vesicles
– multiple types of NTs can be found in one neuron type
http://www.lifesci.ucsb.edu/~mcdougal/neurobehavior/modules_homework/lect3.dcr
Synapses
• NTs will cause either and excitatory or inhibitory response
• If the NT depolarizes the postsynaptic neuron =
excitatory
– Often called an excitatory postsynaptic potential (EPSP)
– Opening of sodium channels or other cation channels (inward)
• Some NTs will cause hyperpolarization = inhibitory
– Often called an inhibitory postsynaptic potential (IPSP)
– Opening of chloride channels (inward) or potassium channels
(outward)
• Neural activity depends on summation of all synaptic
activity
– Excitatory and inhibitory
Synapses
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Chemical
– Membranes of pre and postsynaptic neurons do not touch
– Synaptic cleft exists between the 2 neurons – 20 to 50 nm
– the electrical impulse cannot travel across the cleft – indirect
method is required – chemical messengers (neurotransmitters)
– Most common type of synapse
– The neurotransmitter induces a postsynaptic potential in the PS
neuron – type of AP
– Communication in one direction only
http://www.blackwellpublishing.com/matthews/nmj.html
Chemical
synapse
– Is the conversion of an electrical signal (presynaptic) into a chemical signal
back into an electrical signal (postsynaptic)
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1. nerve impulse arrives at presynaptic end bulbs
2. fusion of synaptic vesicles to PM - role for calcium
3. release of NTs
4. opening of channels in PM of postsynaptic neuron (e.g. sodium)
5. postsynaptic potential develops – depolarization & triggering of AP in
postsynaptic neuron
Chemical synapse
• propagation of AP at the target post-synaptic neuron
usually involves opening of ligand-gated Na+
channels on the membrane of the post-synaptic
neuron
– binding of NT to a receptor on post-synaptic membrane
– this receptor is the ligand-gated channel
Release of NTs from Synaptic end bulbs
-synaptic vesicles are filled with
NTs
-the vesicles move into proximity
near the PM of the end bulb =
active zone
-upon receipt of AP into these bulbs
-causes the opening of voltagegated Ca2+ channels
-the influx of calcium promotes the
“docking” of the synaptic vesicle
with the PM and the exocytosis of
their contents
-the synaptic vesicle components
are recycled for future use
Synaptic vesicles can be
filled, exocytosed, and
recycled within a minute
Synapses
• Electrical
– Direct physical contact between cells required
– Conducted through gap junctions
– Two advantages over chemical synapses
• 1. faster communication – almost instantaneous
• 2. synchronization between neurons or muscle fibers
– e.g. retina, heart-beat
Neurotransmitters
• More than 100 identified
• Some bind receptors and cause channels to open
• Others bind receptors and result in a second
messenger system
• Results in either excitation or inhibition of the target
• Removal of NTs
– 1. Diffusion
• move down concentration gradient
– 2. Enzymatic degradation
• e.g. acetylcholinesterase
– 3/ Uptake by neurons or glia cells
• neurotransmitter transporters
• e.g. NE, epinephrine, dopamine, serotonin
1. small molecules: Acetylcholine (ACh)
• All neuromuscular junctions use ACh
• ACh also released at chemical synapses in the PNS and by
some CNS neurons
• Can be excitatory at some synapses and inhibitory at others
• Inactivated by an enzyme acetylcholinesterase
• Blockage of the ACh receptors by antibodies = myasthenia
gravis - autoimmune disease that destroys these receptors
and progressively destroys the NMJ
– Anticholinesterase drugs (inhibitors of acetylcholinesterase) prevent
the breakdown of ACh and raise the level that can activate the still
present receptors
Neurotransmitters
2. Amino acids: glutamate & aspartate & GABA
– Powerful excitatory effects
– Glutamate is the main excitatory neurotransmitter in the CNS
– Stimulate most excitatory neurons in the CNS (about ½ the
neurons in the brain)
– Binding of glutamate to receptors opens calcium channels = EPSP
– GABA (gamma amino-butyric acid) is an inhibitory
neurotransmitter for 1/3 of all brain synapses
• GABA action is affected by a broad range of drugs called benzodiazepines
– e.g. lorazepan – Ativan
– e.g. diazepam - Valium
• Various uses: hynoptic, sedative, anxiolytic, anticonvulsant, muscle relaxant,
amnesic
• Short lasting – half life is less than 12 hours
– hypnotic effects
– insomnia
• Long lasting – half life is more than 24 hours
GABA
– anxiolytic effects (anti-anxiety drug)
• Acts to enhance GABA
– GABA – major inhibitory NT in the CNS
– GABA binds to GABA receptors – several types
– Benzodiazepines bind and modulate the activity of the GABAA receptor which is
the most prolific NT receptor in the brain
• GABAA receptor is comprised of 5 protein subunits
• One subunit is the alpha subunit
• BZ’s bind to the alpha subunit only and increase its affinity for binding the GABA
neurotransmitter
• The GABAA receptor is a ligand-gated chloride channel
• Binding of GABA increases the inward flow of chloride ions which hyperpolarizes the
neuron and inhibits its ability to make a new action potential
• Therefore BZ’s potentiate the inhibitory effects of GABA
Valium
• top selling drug from 1969-1982
– GABA agonist
– Also decreases the synthesis of neurosteroid hormones (e.g.
DHEA, progesterone) which may regulate emotional state
– Acts on areas of the limbic system, the thalamus and the
hypothalamus (anti-anxiety drug)
– Metabolized by the liver into many metabolites
– Gives rise to a biphasic half live of 1-2 days and 2-5 days!
– Lipid-soluble and crosses the blood-brain barrier very easily
– Stored in the heart, the muscle and the fat
– Some drugs (barbituates), anti-depressants and alchohol can
enhance its effect
– Smoking can increase the elimination of valium and decrease its
effects
Neurotransmitters
3. Biogenic amines: modified amino acids
– catecholamines: norepinephrine (NE), epinephrine, dopamine (tyrosine)
– serotonin - concentrated in neurons found in the brain region = raphe
nucleus
• derived from tryptophan
• sensory perception, temperature regulation, mood control, appetite, sleep
induction
• feeling of well being
– NE - role in arousal, awakening, deep sleep, regulating mood
– epinephrine (adrenaline) - flight or fight response
– dopamine - emotional responses and pleasure, decreases skeletal muscle
tone
Other types:
a. ATP - released with NE from some neurons
b. Nitric oxide - formed on demand in the neuron then release (brief lifespan)
-role in memory and learning
-produces vasodilation
• Involved in feelings of pleasure, strength
• Also mediates skeletal muscle contraction
• Neurotransmitters like dopamine, serotonin, glutamate, acetylcholine
etc… are secreted and then rapidly internalized by transporters in order to
control their levels within the nervous system
• Many drugs affect these transporters
• Ritalin = methylphenidate
Dopamine
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Stimulant used to treat ADD, ADHD, narcolepsy amd chronic fatigue
1954 – initially prescribed for depression and narcolepsy
1960 – prescribed to children with ADD, ADHD
Reason?? Might be due to an imbalance in dopamine
Binds both dopamine and norepinephine transporters and inhibits their ability
to take these NTs back up (keeps their levels high in the synapse)
– Dopamine transporters (DAT) found in the PM of neurons (presynaptic)
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Transports dopamine back into the neuron along with sodium ions (symporter)
This terminates the dopamine signal
Chloride ions are also required to enter the neuron to prevent depolarization
In adults – these transporters regulate dopamine levels
• Cocaine – binds and inhibits DATs – increasing dopamine in the synapse
• Amphetamines – binds amphetamine receptors on a neuron which
causes the internalization of the DAT into the neuron – increasing
dopamine in the synapse
Neuropeptides
• widespread in both CNS and PNS
• excitatory and inhibitory
• act as hormones elsewhere in the body
-Substance P -- enhances our perception of pain
-opioid peptides: endorphins - released during stress, exercise
-breaks down bradykinins (pain chemicals), boosts
the immune system and slows the growth of cancer
cells
-binds to mu-opioid receptors
-released by the neurons of the Hypothalamus and by
**acupuncture
the cells of the pituitary
may produce loss
enkephalins - analgesics
of pain sensation
-breaks down bradykinins (200x stronger than morphine)
because of release
-pain-relieving effect by blocking the release of
of opioid-like
substance P
substances such as
dynorphins - regulates pain and emotions
endorphins or
dynorphins
Morphine
• Opiate analgesic
• Principal agent in opium
– Acts on the CNS
– Acts on the GI tract – decrease motility, decrease gastric secretion,
decreases gastric empyting, increases fluid absorption
• Other opiates: heroin, codeine, thebaine
• Acts on the neurons of the CNS (specifically the nucleus accumbens of
the basal ganglia)
• Binds to the mu-opioid receptor
– Found throughout the brain – especially in the posterior amygdala, the
hypothalamus and thalams, the basal ganglia, the dorsal horn of the spinal
cord and the trigeminal nerve
– Relieves the inhibition of GABA release by presynaptic neurons
– Also relieves the inhibition of dopamine release (addiction)
– Binding activates the receptor and gives rise to: analgesia, euporia,
sedation, dependence and respiratory and BP depression.
• Acts on the immune system! – increase incidence of addiction in those
that suffer from pneumonia, TB and HIV
– Activates a type of immune cell called a dendritic cell – decrease their
activation of B cells – decreased antibody production – decrease immune
function