P1253814566VpzBg

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• Nervous System
•  Neurons
• Carry out sensory and motion functions
• Sense the physical and chemical stimuli
• Make responses by sending out nerve
• impulses.

Neuroglial cells - provide structure frame and
nutrition supply to neurons.
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  Nervous system ? CNS brain and spinal
cord PNS nerves and sensory
organs   General functions sensory,
Integration, Motor.  
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Changes of the inside and outside environment
are detected by sensory receptors, and converted
into electrical impulses by sensory neurons .
The nerve impulses are transmitted to the CNS
where the signals are integrated and decisions
are made. Responses are sent out to the
related body parts through motor neurons.
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The peripheral responsive organs are called
effectors (muscles and glands).  
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Structure of a Neuron 1. Cell body Mostly
located in CNS. 2. Dendrites - short and
branched, receive and transmit signal to the
cell body. 3. Axons - long and usually single,
conduct impulses away from the cell body
contain many mitochondrias.
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Types of neurons (Based on functions) 1,
Sensory (or afferent) neurons Have receptors on
the tip of dendrites, conduct signals from the
receptors to the CNS. 2. Interneurons (or
association neurons) Located in brain and spinal
cord (CNS) transmit incoming signals to
different parts of CNS and transfer the outgoing
signals to motor neurons.
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3. Motor (or efferent) neurons Carry nerve
impulses out from CNS to effector organs
(muscles and glands).   Two types of motor
neurons Somatic motor neuron - responsible for
skeletal muscles activities. Autonomic motor
neurons - control the activities of internal
organs and glands. Their cell bodies are
located outside of CNS in autonomic
ganglia. (See overhead)
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Supporting Cells In PNS Schwann cells -
wrapping around axons to form insulation Sat
ellite cells, or ganglionic gliocytes - support
cell bodies in ganglia.  
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In CNS Oligodendrocytes - form myelin sheath
around axons in CNS Microglia phagocytic,
engulf foreign substances and damaged cells.
Astrocytes - star like cells that fill out the
space between neurons. Ependymal cells -
line the ventricles (cavities in brain and
spinal cord).
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•  Schwann Cells and Myelin Sheath
• Form a coating for axons in PNS. The
• chemical composition of this coating is
• basically lipoprotein called myelin.
• The nerve fibers wrapped by myelin sheets
• are called myelinated fibers.
• The main function is insulation. So the
• impulse transmission can occur faster.

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Gaps between Schwann cells are known as nodes of
Ranvier, which allows nerve impulses to be
transmitted in a skipping way.
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Myelin sheath in CNS (oligodendrocytes) Since
the myolin sheath has white color, the areas in
CNS that have high concentration of axons are
called white matter. Those with high
concentration of cell bodies are called gray
matter (cerebral cortex).
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Electrical Activity in Axons (p139 - p143) How
are nerve impulses formed?   All animal bodies
have bio-electricity, which is related with
  Cell membrane potential - charge difference
between the inside and outside of cell membrane.

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What causes charge difference between the inside
and outside of the membrane? - Uneven ion
distribution.   Concentration of Na is higher
outside of the cell, and lower inside. The
distribution of K is opposite. Na/K pump
constantly pumps Na ions from inside to
outside, and K from outside to inside (ion
exchange 3 Na out, 2 K in).  
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  In cytoplasm, there are negatively charged
ions Cl-, PO4 and SO4,.   The high
concentration of Na outside and high
concentration of negatively charged ions inside
create a charge difference between the two sides
of the cell membrane, ( K inside is not
sufficient to neutralize the negative charge of
the anions).
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Membrane potential is largely determined by the
membrane permeability. Na/K pump also
contributes to the negative charge inside the
cell (3 Na out, only 2 K in).   Potential
energy of position. The chemical gradient of
ions creates a resting potential.
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Electrical Activity of cells depends on cell
membrane potential charge difference existing
between the two sides of the cell
Membrane. Resting potential cytoplasm is
slightly negative, extracellular environment is
slightly positive.
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The resting membrane potential of most cells
ranges from -65 mV to -85 mV. The negative
mark indicates the negative polarity of
cytoplasm.  
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All cells have a membrane potential, but only a
few types can change membrane potential in
response to stimulation.
These are called excitable cells (muscle and
nerve cells). The change in membrane
potential is due to the change in membrane
permeability to certain ions. Ion channels
play a key role
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When a nerve cell is not stimulated, the
membrane potential is called resting potential,
and the cell membrane is polarized.   Depolarizat
ion decrease in resting potential (outside
less positive and inside less negative).
Repolarization - restoration of negative
membrane potential.
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•  Ion Channels
• The gates on membrane that allow ions to
• flow through.
• These channels are highly specific.
• When depolarization occurs, Na and K
• channels are open, which allows Na to flow
• out and K flow in down their concentration
• gradients.

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Two types of K channels One type is slow but
always open (the membrane is more permeable to K
than to Na). The other type is closed during
resting status.
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Action Potential When cell membrane is
stimulated 1. Na permeability increases ? Na
start to diffuse in ? inside less
negative ? membrane start to depolarize.
2. When depolarization reaches to a threshold,
Na channels open ? Na influx ? potential
reverses it changes from -70 to 30 mV.
(The Na channel is voltage regulated.)
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3. K channels open ? K efflux ? positive
charge is rebuilt outside of the cell
membrane cytoplasm becomes negative
again. Repolarization allows the cell membrane
to return to resting potential (-70 mV). From
depolarization to repolarization - msec.
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• Polarization resting potential,
• ( outside, - inside)
• Depolarization related with action potential,
• (- outside, inside)
• Repolarization restoration of resting
  potential.
• ..

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An action potential is the potential change in a
small region of cell membrane. Multiple action
potentials form a nerve impulse.
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All or None Law Once depolarization reaches the
threshold, the membrane potential shoots to the
limit, 30 mV
The magnitude and length of the time is
independent of the strength of the stimulation.
  Therefore the amplitude of action potential is
said to be all or none.
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From -70 mV to 30 mV to -70 mV lasts 3 msec.
(Overhead)
The amplitude of action potential is about the
same in all neurons at all times.
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Refractory periods During the time when a region
of membrane is producing action potential, it is
not able to respond to another stimulus. The
cell membrane is said to be refractory.
Cardiac muscle cells have long refractory
period, therefore, two contractions will not
overlap.
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Absolute refractory period - during action
potential. Relative refractory period -during
depolarization, a very strong stimulus can
overcome the depolarization and produce a
second action potential.
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Nerve Impulse Depolarization of one region of a
nerve fiber will create a charge difference
between two adjacent regions. See overhead.
The local current will stimulate the adjacent
membrane to have action potential, which Will
trigger another action potential in the next
area
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A wave of action potentials will move down the
nerve fiber to form an electrical current -
nerve impulse.
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• How are the impulses conducted?
• In a myolinated axon
• Ion channels only exist in the gaps between
• Schwann cells.

• Action potential is therefore only produced
• in the nodes of Ranvier.
• Axon has cable like activity to conduct the
• electric current, so the impulses leap from
• node to node (Fig. 7.17).

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Conduction Between Cells Synapse the
functional connection between neurons or between
a neuron and an effector cell.
A. Gap junctions electrical synapse Numerous
channels run through the junction to allow ions
and molecules to flow through. Gap junctions
in cardiac muscle ensure coordinated contraction.
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B. Chemical Synapse More often the conduction of
impulses between cells is chemical.  
Chemical synapse can exist in the form
of a. Axon - dendrite, b. Axon - cell body,
c. Axon - axon, d. Axon - effector cell
(For example, a neuromuscular junction)
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A chemical synapse involves a presynaptic
membrane (axon) and a postsynaptic membrane.
Synaptic cleft - space between presynaptic
and postsynaptic membranes.
Neurotransmitters chemicals messengers
released by the presynaptic cell, cross the
cleft and reach the postsynaptic membrane.
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The traveling of neurotransmitters across the
synapse is usually one way. Only the ends of
axons contain synaptic vesicles.
Vesicles containing neurotransmitters
are released by exocytosis when a nerve impulse
reaches the nerve end. Overhead
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The messenger released by a motor neuron to
excite skeletal muscles is acetylcholine (ACh).
Other neurotransmitters epinephrine (also
know as adrenaline), norepinephrine, dopamine
and serotonin etc.  
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Based on the types of neurotransmitters that the
nerve ending release, neurons are divided into
cholinergic sand adrenergic. The binding between
neurotransmitter and receptor causes the
membrane permeability of postsynaptic membrane
to change...
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Two categories of ion channels
Voltage regulated channels -respond to
membrane depolarization Chemical regulated
channels -respond to neurotransmitters.
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The opening of chemical regulated ion channels
may lead to two different consequences.
Excitatory and inhibitory actions Opening of
some ion channels produce depolarization -
excitatory postsynaptic potential (EPSP). Some
will cause hyperpolarization (the inside
becoming more negative) - inhibitory
postsynaptic potential (IPSP).
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• EPSP will stimulate the postsynaptic cell
• to produce action potential and cause
• excitatory effect.
• IPSP will prevent action potential and
• cause relaxation effect.

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•  
• Generally, adrenaline and dopamine
• transmit excitatory actions, and serotonin
• transmits inhibitory actions.
• ACh, can produce either effects depending
• on different target organs.

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The post-synaptic cells that able to respond to
the excitatory neurotransmitters are called
excitable cells. For exp. muscle cells.  
Once action potential is induced, it is
immediately propagated and the nerve impulse is
passed along.
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Actylcholine (ACh) The nerve fibers that secrete
ACh are cholinergic nerve fibers.   The
postsynaptic effect of ACh can be both
excitatory and inhibitory. .. In skeletal
muscle, ACh's effect is excitatory, but in CNS
it can be either excitatory or inhibitory.  
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Two subtypes of ACh receptors Nicotinic
receptor - located on the cell membrane of
skeletal muscles, and can be the binding site
for nicotine. Muscarinic receptor located on
other cells, and can be bond by muscarine, a
toxin from some mushrooms.
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 Nicotinic ACh receptor A protein complex that
encloses ion channels. The channels open when
ACh binds to the receptor, which allows Na to
diffuse in and K diffuse out simultaneously. Fig
. 7.23 on p 170
Na influx is predominant, which leads to
depolarization.
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Due to the constant K leaking, the
postsynaptic membrane potential will not shoot
to 30 mV as in action potential. Its
magnitude depends on the amount of
neurotransmitters released (what happens in
skeletal muscle).
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The postsynaptic depolarization induced by ACh
does not have a threshold and is not all or
none. It has no refractory period, so
depolarization of several EPSP can be added
together.
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 G protein-operated channels Muscarinic
receptors are not associated with ion channels.
Binding of ACh to muscarinic receptors
activates G-protein, which is a complex of ?,
?, and ? subunits.
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• Upon activation, ?, or ? subunits migrate to
• K channels and make them open.
• K efflux produce hyperpolarization of the
• postsynaptic membrane.
• For example, in the heart, the ? subunit causes
• the opening of K channel and IPSP of cardiac
• muscle cell, cardiac muscle activity is inhibited

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Neuromuscular junction - synapse between a
motor neuron and skeletal muscle. Motor end
plate - postsynaptic membrane of a muscle cell.
  Binding of ACh to the receptors on motor end
plate produces EPSP called end-plate potential,
which opens the voltage-regulated channels to
create an action potential.  
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 Muscle weakness in myasthenia gravis -autoimmune
disease ACh receptors are attached by
antibodies Skeletal muscles contraction is
blocked.
ACh is also important neurotransmitter involved
in the functions of parasympathetic nervous
system (details later).
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Acetylcholinesterase (AChE) After the action,
some neurotransmitters are decomposed by enzymes
that exist in synaptic cleft. Some are
recycled back to the nerve endings and will be
reused for the next action.
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After the dissociation of ACh-receptor
complex,the free ACh is inactivated
acetylcholinesterase (AChE). This enzyme can
be inhibited by nerve gas or tetanus toxin,
which leads to skeletal muscle spasm - spastic
paralysis.
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Clinically, AChE inhibitors have been used to
treat certain neural system diseases including
skeletal muscle weakness. Alzheimers disease
has been noticed to be associated with the loss
of cholinergic neurons In CNS. AchE has been,
therefore, used for the disease to augment
cholinergic transmission in the brain.
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  Monoamines as Neurotransmitters   Monoamines
are a group of molecules that are derived from
single amino acids. For example, serotonin is
a derivative of tryptophan. Epinephrine,
norepinephrine and dopamine (catacholamines) are
derivatives of tyrosine.
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Epinephrine and norepinephrine are very similar
in structure and function. They have similar
target organs and physiological
effects. Epinephrine (adrenaline) is produced by
adrenal gland as a hormone. Norepinephrine is
both hormone (adrenal cortex also secrete small
amount of NA) and neurotransmitter (mainly
produced by adrenergic neurons.)
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Inactivation of monoamine neurotransmitters
a.     Reuptake by the presynaptic neuron
(serotonin) b.     Enzymatic degradation in the
presynaptic neuron c.     Enzymatic
degradation in the postsynaptic neuron.
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Serotonin

• Involved in the regulation of mood, behavior,
• appetite and cerebral circulation.
•  
• Serotonin Specific Reuptake Inhibitors
• (SSRI) have been used to treat depression,
• anxiety, obesity and migraine headache
• For exp.Selexa, an antidepressant, inhibits
• the reuptake of serotonin to decrease its
• degradation and increase the half life in
• the brain.

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The action of monoamine neurotransmitters is
mediated by intracellular secondary messengers.
One typical secondary messenger is cyclic
AMP.  
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• Binding of epinephrine or norepinephrine to
• their receptors ? dissociation of G-protein
• ?-subunit migrate to adenylate cyclase
• ATP cAMP.

adenylate cyclase

• cAMP ? protein kinase ? protein P-tion
• opening of ion channels in postsynaptic
• membrane ...

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• This series of intracellular events are called
• signal transduction pathway. Fig. 7.28.

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Dopamine Is also involved in the regulation of
mood and emotion. Neurons producing dopamine
are called dopaminergic neurons. Two different
dopamine systems Nigrostriatal system involved
in motor control Mesolimbic system - emotion
reward.
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Nigrostriatal dopamine system is located in
basal nuclei deep in the cerebrum. Its
function is the initiation of skeletal
movement. Parkinson's disease may be related
to the degradation of nigrostriatal system.  
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Current treatment administration of L-Dopa
(precursor of dopamine) and MAO inhibitor that
slows down the degradation of dopamine. (read the
blue box on p175) Why use L-Dopa, instead of
dopamine, read Blood-brain Barrier on p158!
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  Mesolimbic Dopamine System Neurons located in
mid-brain, sending axons to limbic system (where
high concentration of dopamine is found).
Mesolimbic system is what involved in
emotional rewarding.
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Drugs such as alcohol, morphine, heroin,
cocaine, amphetamines, marijuana and nicotine
can increase the release of dopamine by
dopaminergic neurons and cause euphoria.
Cocain also blocks the reuptake of
dopamine. The drug addiction caused by the above
substances is basically due to rewarding
characteristic of dopamine action.
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Withdrawal symptoms of drug abuse Drug use
leads the brain and other organs to reach a new
chemical balance. (The body is dependent on
drugs to maintain the normal levels of dopamine,
serotonin, and norepinephrine). When drug is
absent, the body would show the symptoms for
depleted neurotransmitters. If the drug is a
stimulant such as cocaine. The symptoms would be
craving for the drug, depression, drowsiness,
agitation... If the drug is a depressants
(sedative effect) anxiety..
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Norepinepherine and Epinephrine are also involved
in general well being, behavior and mood.
Amphetamine mimics epinephrine and
norepinepherine's effects and can cause
increased mental arousal, self-confidence,
alertness, increased blood pressure and
heartbeat ...  
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  Amino acids as neurotransmitters Some act as
excitatory transmitter, such as glutamate and
aspartate. Some work as inhibitory transmitter
such as glycine. P178  
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NMDA receptor - One type of glutamate receptor,
is involved in memory storage.
Long term potentiation When a presynaptic neuron
is stimulated at a high frequency, the
excitability of the synapse is enhanced (or
potentiated), which can last for hours or even
weeks.   LTP may favor transmission of
frequently used neural pathways and represent a
mechanism of neural learning and memory.
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GABA gamma-aminobutyric acids is a
derivative of glutamate. One third of the
neurons in the brain use GABA as
neurotransmitter. GABA has inhibitory effect in
the CNS and is also involved in motor
control. Valium (a benzodiazepine drug) enhances
GABAs effect to induce sedative effect
and relief muscle spasm.
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Polypeptides -  endogenous opioids Opium and
it's analogs can kill pain and cause euphoria by
binding to morphine receptors in limbic system.
Morphine receptor or opioid receptor was
discovered in 1973.
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Brain produces a group of similar chemicals that
mimics morphine's analgesic and euphoric
effects. The most well known one is
?-endorphin, another is a group called
enkaphalins, and the third is dynorphin. The
secretion and activation of these peptides can
be stimulated by stress, pain and exercise.
For example, secretion of ?-endorphin can be
greatly increased in a pregnant woman before
childbirth.
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  Like morphine, endorphin can cause euphoria
and increase the threshold of pain sensation in
the brain. Endorphin level was found to be high
after exercise, this may explain why exercise
can reduce anxiety and give a feeling of
wellbeing (jogger's high).        
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Morphine or Heroine abuse suppresses bodys
ability to produce endorphin.
Withdrawal symptoms depression, anxiety, running
nose, yarning, vomiting, body aches, stomach
cramps, diarrhea, increased heartbeat or
arrhythmia The whole autonomic nervous System
is disturbed.