Transcript Document

THE NERVOUS
SYSTEM: NEURAL
TISSUE
Two organ systems coordinate and
direct activities of body
• Nervous system
– Swift, brief responses to stimuli
• Endocrine system
– Adjusts metabolic operations
– Directs long-term changes
An Overview of the Nervous System
Divisions of the nervous system
Anatomical Classification of the
Nervous System
• Central Nervous System
– Brain and spinal cord
• Peripheral Nervous System
– All neural tissue outside CNS
Functional divisions of nervous
system
• Afferent
– Sensory information from receptors to CNS
• Efferent
– Motor commands to muscles and glands
– Somatic division
• Voluntary control over skeletal muscle
– Autonomic division
• Involuntary regulation of smooth and cardiac muscle, glands
Histology of Neural Tissue
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
• Largest of glial cells
• Star shaped with many processes
projecting from the cell body
• Help form and maintain blood-brain barrier
• Provide structural support for neurons
• 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
• Assist in neuronal migration during brain development
• Perform repairs to stabilize tissue
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 = 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 cell bodies
• Support neurons in the PNS
PNS: Schwann Cells
Neurilemma
• 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
Representative Neuron
1. cell body or soma
-single nucleus with prominent nucleolus
-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
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
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) 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
The electric potential across an axonal
membrane can be measured
• the differences in positive and
negative charges in and out
of the neuron can be measured by
electrodes = resting membrane potential
-ranges from -40 to -90 mV
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
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
The action potential
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1. neuron is at resting membrane potential (resting MP)
2. neuron receives a signal
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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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Inside of neuron (i.e. MP) becomes more positive
6. if neuron depolarizes enough to Threshold = Action
Potential (AP)
7. 1st stage of AP – opening of voltage-gated Na channels
8. even more Na flows in through VGNa channels = BIG
depolarization
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3. NT binds ligand-gated sodium channel
4. LGNa channel opens
5. Na flows into neuron = depolarization
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Neurotransmitter (NT)
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
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Continuous versus Saltatory Conduction
• Continuous conduction
(unmyelinated fibers)
– An action potential spreads
(propagates) over the surface of
the axolemma
– as Na+ flows into the cell
during depolarization, the
voltage of adjacent areas is
effected and their voltage-gated
Na+ channels open
– step-by-step depolarization of
each portion of the length of
the axolemma
http://highered.mcgrawhill.com/sites/0072437316/student_view0/chapter45/animations.html#
Saltatory Conduction
• Saltatory conduction
(myelinated fibers)
-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 flowing
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
Synaptic Communication
Synapses
Synapse: Site of intercellular communication between 2
neurons or between a neuron and an effector (e.g.
muscle – neuromuscular junction)
• Permits communication between neurons and other cells
– Initiating neuron = presynaptic neuron
– Receiving neuron = postsynaptic neuron
• You can classify a synapse according to:
– 1. the action they produce on the post-synaptic neuron –
excitatory or inhibitory
– 2. the mode of communication – chemical vs.
electrical
Synapses – Excitatory vs. Inhibitory
• If the NT depolarizes the postsynaptic neuron =
excitatory
– The depolarization event is often called an excitatory
postsynaptic potential (EPSP)
– Opening of sodium channels or other cation channels (inward)
• Some NTs will cause hyperpolarization = inhibitory
– The hyperpolarization event is 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
• 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. heart beat
Chemical Synapse
• Synapse
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Most are axodendritic axon -> dendrite
Some are axoaxonic – axon > axon
http://www.lifesci.ucsb.edu/~mcdougal/neurobehavior/modules_homework/lect3.dcr
Synapses – Chemical vs. Electrical
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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 – if the potential is an EPSP – excitatory and an AP
results (e.g. glutamate)
• If the potential is an IPSP – inhibitory and NO AP results (e.g.
glycine or GABA)
– Communication in one direction only
http://www.blackwellpublishing.com/matthews/nmj.html
The Events in Muscle Contraction
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AP generated at trigger zone in
pre-synaptic neuron
AP arrives in end bulb – causes entry
of calcium into end-bulb – release
of Ach
Binding of Ach to ligand-gated Na
channels on muscle PM (Ach receptors)
Na enters muscle cell – depolarization
Muscle membrane potential reaches
threshold = Action Potential
AP travels through PM of muscle cell into
T-tubules
AP “passes by” sarcoplasmic reticulum –
release of calcium into muscle cell
Ca binds troponin-tropomyosin complex &
“shifts” it off myosin binding site
Cross-bridging between actin and myosin,
pivoting of myosin head = Contraction
(ATP dependent)
The Neuromuscular Junction
• end of neuron (synaptic terminal or
axon bulb) is in very close association
with the muscle fiber
• distance between the bulb and the folded
sarcolemma = synaptic cleft
• nerve impulse leads to release of
neurotransmitter (acetylcholine)
• N.T. binds to receptors on myofibril
surface
• binding leads to influx of sodium,
potassium ions (via channels)
• eventual release of calcium by
sarcoplasmic recticulum = contraction
• Acetylcholinesterase breaks down ACh
• Limits duration of contraction
Motor Units
• Each skeletal fiber has only ONE
NMJ
• MU = Somatic neuron + all the
skeletal muscle fibers it innervates
• Number and size indicate precision of
muscle control
• Muscle twitch
– Single momentary contraction
– Response to a single stimulus
• All-or-none theory
– Either contracts completely or not at
all
• Motor units in a whole muscle fire asynchronously
some fibers are active others are relaxed
delays muscle fatigue so contraction can be sustained
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Muscle fibers of different motor units are intermingled so that net distribution of force
applied to the tendon remains constant even when individual muscle groups cycle
between contraction and relaxation.
Motor Tone
• Resting muscle contracts random motor
units
– Constant tension created on tendon
– Resting tension – muscle tone
• Stabilizes bones and joints
Neurotransmitters
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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
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
Neurotransmitters
2. Amino acids: glutamate & aspartate & GABA
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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
– MSG – monosodium glutamate
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flavor enhancer since 1900’s
used as a purified salt of L-glutamic acid or in a mixture of amino acids
intermediate in amino acid metabolism, energy source for cardiac myocytes
can cause Chinese Restaurant syndrome – numbness, muscle weakness and heart
palpitations – similar to effects seen upon Ach administration
• MSG can be converted into ACh via the Citric acid cycle
• ACh in the CNS is involved in memory, arousal and reward – excitatory NT
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
Removal of Neurotransmitter
• Enzymatic degradation
– acetylcholinesterase
• Uptake by neurons or glia cells
– neurotransmitter transporters
• NE, dopamine, serotonin
• 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
Dopamine
• 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
– 1954 – initially prescribed in adults for depression and narcolepsy stimulant
– 1960 – prescribed to children with ADD, ADHD - depressant
– 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
**acupuncture
-binds to mu-opioid receptors
may produce loss
-released by the neurons of the Hypothalamus and by
of pain sensation
the cells of the pituitary
because of release
of opioid-like
enkephalins - analgesics
substances such as
-breaks down bradykinins (200x stronger than morph
endorphins or
-pain-relieving effect by blocking the release of
dynorphins
substance P
dynorphins - regulates pain and emotions
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