lecture #6

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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
• 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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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
Two types in the PNS
– Schwann cells
– Satellite cells
• 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
-processes make contact with the capillaries supplying
CNS tissue, CNS neurons and the pia mater membrane
covering the brain and spinal cord
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Help form and maintain blood-brain barrier
– processes wrap around the blood capillaries and isolate the
neurons from their blood supply
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Provide structural support for neurons
Maintain the appropriate chemical environment for generation of nerve
impulses/action potentials
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regulate ion concentrations - generation of action potentials by neurons
Take up excess neurotransmitters from the synapse
Regulate nutrient concentrations for neuron survival
Assist in neuronal migration during brain development
Perform repairs to stabilize tissue – scar formation???
Oligodendrocytes
• Most common glial cell
type
• Each forms myelin
sheath around the axons
of neurons in CNS
• Analogous to Schwann
cells of PNS
• Form a supportive
• fewer processes than astrocytes
network around CNS
• round or oval cell body
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
Phagocytic role - clear away dead cells
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 = colorless 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
• Found in the ganglia of the PNS
PNS: Schwann Cells
• each cell surrounds multiple unmyelinated PNS axons with a single
layer of its plasma membrane
• produces part of the myelin sheath surrounding an axon in the PNS
• also contributes to 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
-neurofilaments give cell shape and support –also
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 – either with
their axons of cell
bodies
3. Cell processes = axons
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conduct impulses away from cell body
toward synaptic end bulbs
• sites for neurotransmitter storage
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 the location for most protein synthesis
– neurotransmitters & repair proteins
• however the axon or axon terminals require neurotransmitters for
signaling
• Axonal transport system moves substances to the synaptic terminals
– slow axonal flow
• movement of axoplasm in one direction only -- away from cell body to the
terminals
• only 1-5 mm per day
• replenishes axoplasm in regenerating or maturing neurons
– fast axonal flow
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moves organelles & neurotransmitters via microtubules
at 200-400 mm per day
transports material in either direction
for transport to the terminals or for recycling things back to the cell body
Structural Classification of Neurons
•
can classify neurons two main ways:
– 1. Structural
– 2. Functional
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1. 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)
Structural Classification of Neurons
• 2. or can classify by the name of the histologist that first described
them
•Purkinje = cerebellum
•Renshaw = spinal cord
• 3. or can classify them by their appearance
– e.g. pyramidal neurons
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
• polarization – change in membrane potential away
from resting MP
– 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
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
-so K+ leakage is the main factor in setting the resting membrane potential
2. Gated channels: channels can possess gates to open and close them
-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
Action Potential
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Resting membrane potential is 70mV
AP is triggered when the
membrane potential reaches and
exceeds a threshold (usually -55
MV)
action potential = nerve impulse
takes place in two stages: depolarizing phase (more positive – e.g. -70 mV to -60mV)
and repolarizing phase (more negative - back toward resting potential – e.g. + 30 mV
to +20 mV)
followed by a hyperpolarizing phase or refractory period in which no new AP
can be generated
The action
potential
9.
http://www.blackwellpublishing.c
om/matthews/channel.html
8.
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1. neuron is at resting membrane potential (resting MP)
2. neuron receives a signal
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1.
11.
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2 & 3.
Inside of neuron (i.e. MP) becomes more positive
Membrane potential goes from negative to positive
9. closing of VGNa channels & opening of voltage-gated K channels
10. BIG outflow of potassium through VGK channels = repolarization
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4. & 5.
6. if neuron depolarizes enough to Threshold = Action Potential (AP)
7. 1st stage of AP – opening of voltage-gated Na channelsc(VGNa)
8. even more Na flows in through VGNa channels = BIG depolarization
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6 & 7.
Neurotransmitter (NT)
3. NT binds ligand-gated sodium channel (LGNa)
4. LGNa channel opens
5. Na flows into neuron = depolarization
10.
Inside of neuron (MP) becomes more negative
11. neuron repolarizes so much – it goes past resting and hyperpolarizes
12. closing of VGK channels
13. all voltage-gated channels closed, Na/K pump “resets” ion distribution to
resting situation
13.
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
again and K+ channels close. This
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+ channels close and
the MP becomes more negative returning toward
resting MP
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
• not related to stimulus strength
• Properties of axon
• Presence or absence of myelin sheath
– myelin = 5 to 7X faster
• Diameter of axon
– larger = faster conduction
Action Potentials in Nerve and Muscle
• another excitable cell type = muscle
• muscle cells can generate their own action potential in response
to the neuron’s
• are some notable differences vs. Neurons
• 1. entire muscle cell membrane versus only the axon of the
neuron is involved
• 2. resting membrane potential differ
– nerve is -70mV
– skeletal & cardiac muscle is closer to -90mV
• 3. AP duration is longer in muscles
– nerve impulse is 1/2 to 2 msec
– muscle action potential lasts 1-5 msec for skeletal & 10-300msec for
cardiac & smooth
• BUT fastest nerve conduction velocity is 18 times faster than
velocity over skeletal muscle fiber
Synaptic Communication
Synapse
• Synapse
– 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
• site of neurotransmitter release
– 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 in the
post-synaptic neuron
• If the NT depolarizes the postsynaptic neuron = excitatory
– change in membrane potential is called an excitatory postsynaptic potential
(EPSP)
– produced through the opening of sodium channels or other cation channels
(inward)
• Some NTs will cause hyperpolarization = inhibitory
– 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
• 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
• either an EPSP or an IPSP
– 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 in this fusion
3. release of NTs
4. opening of channels in PM of postsynaptic neuron (e.g. sodium)
5. postsynaptic potential develops – possible depolarization & triggering of AP in
postsynaptic neuron
Release of NTs from Synaptic end bulbs
• upon arrival of the AP into the
synaptic end bulbs  the
opening of voltage-gated Ca2+
channels
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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
then 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
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More than 100 identified
produced by neurons and stored
within the neuron
secrete these NTs in response to
generation of an electrical signal
(action potential) by the neuron
bind onto post-synaptic neurons
(synapse) or target muscle cells
(neuromuscular junction)
some bind receptors on the target
and cause channels to open in the
target (e.g. ligand-gated sodium
channels)
others bind receptors on the postsynaptic neuron and result in the
opening of LG channels through
other mechanisms
• result in either excitation
or inhibition of the postsynaptic neuron
Neuromuscular junction
Neurotransmitters
• an important thing to consider is the removal of the
neurotransmitter from the synaptic cleft
• Removal of NTs
– 1. Diffusion
• move down concentration gradient out of the synaptic cleft
– 2. Enzymatic degradation of the NT
• e.g. acetylcholinesterase
– 3. Uptake of the NT by neurons or glial cells (like
astrocytes)
• done by neurotransmitter transporters
• e.g. NE, dopamine, serotonin
Neurotransmitters
1. small molecules: Acetylcholine (ACh)
-All neuromuscular junctions use ACh – can only be excitatory
-ACh also released at chemical synapses between two neurons
-can be excitatory or inhibitory – depends on location and the
neurons involved
-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
– most have powerful excitatory effects
– stimulate most excitatory neurons in the CNS (about ½ the
neurons in the brain)
– GABA (gamma amino-butyric acid) is an inhibitory
neurotransmitter for 1/3 of all brain synapses
• i.e. inhibits the generation of an action potential by the target neuron
- Valium is a GABA agonist - enhances its inhibitory effect
Neurotransmitters
3. Biogenic amines: modified amino acids
– catecholamines: norepinephrine (NE), epinephrine, dopamine, thyroxin
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all derived from the amino acid tyrosine
NE - role in arousal, awakening, deep sleep, regulating mood
epinephrine (adrenaline) - flight or fight response
dopamine - emotional responses and pleasure, decreases skeletal muscle tone
– serotonin: derived from tryptophan
• sensory perception, temperature regulation, mood control, appetite, sleep
induction
• feeling of well being
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 - Viagra enhances the effect of NO
Mimicking or Inhibiting NTs
• Parkinsons - muscle stiffness due to degeneration of dopanergic nerves  loss of
dopamine in the brain  loss of the brain’s control over skeletal muscles
•patients given L-Dopa (dopamine precursor)
• NT release can be enhanced or blocked
•some amphetamines can promote dopamine and NE release
•botulism causes paralysis through blockage of ACh release from motor
neurons
• NT receptors can be blocked or activated
•isoproterenol binds to epinephrine receptors
- used in asthma to mimic the effects of epinephrine
• schizophrenia – caused by an excess of dopamine
•Zyprexa blocks dopamine and serotonin receptors
-antagonizes the effects of serotonin and dopamine
• NT removal/uptake can be promoted or inhibited
•cocaine: blocks transporters for dopamine reuptake
•Prozac, Paxil: blocks transporters for serotonin reuptake
Neuropeptides
• widespread in the nervous system
• excitatory and inhibitory
• act as hormones elsewhere in the body
-Substance P -- enhances our perception of pain
-opioid peptides: endorphins - release during stress, exercise
enkephalins - analgesics
(200x stronger than morphine)
-pain-relieving effect by blocking the release of
substance P
dynorphins - regulates pain and emotions
**acupuncture may produce loss of pain sensation because
of release of opioid-like substances such as endorphins or
dynorphins

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