Human Antatomy &
Physiology
Nervous Tissue
Chapter 12
By
Abdul Fellah, Ph.D
12-1
Copyright (c) The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Nervous Tissue
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
• overview of the nervous
system
• properties of neurons
• supportive cells
(neuroglia)
• electrophysiology of
neurons
• synapses
Neurofibrils
• neural integration
(d)
Figure 12.4d
Axon
12-2
Overview of Nervous System
• endocrine and nervous system maintain internal
coordination
– endocrine system - communicates by means of chemical
messengers (hormones) secreted into to the blood
– nervous system - employs electrical and chemical means to send
messages from cell to cell
• nervous system carries out its task in three basic steps:
• sense organs receive information about changes in the body
and the external environment, and transmits coded messages
to the spinal cord and the brain
• brain and spinal cord processes this information, relates it to
past experiences, and determine what response is appropriate to
the circumstances
• brain and spinal cord issue commands to muscles and gland
cells to carry out such a response
12-3
Two Major Anatomical Subdivisions of
Nervous System
• central nervous system (CNS)
– brain and spinal cord enclosed in bony
coverings
• enclosed by cranium and vertebral column
• peripheral nervous system (PNS)
– all the nervous system except the
brain and spinal cord
– composed of nerves and ganglia
• nerve – a bundle of nerve fibers (axons)
wrapped in fibrous connective tissue
• ganglion – a knot-like swelling in a nerve
where neuron cell bodies are concentrated
12-4
Sensory Divisions of PNS
• sensory (afferent) division – carries sensory
signals from various receptors to the CNS
– informs the CNS of stimuli within or around the body
– somatic sensory division – carries signals from
receptors in the skin, muscles, bones, and joints
– visceral sensory division – carries signals from the
viscera of the thoracic and abdominal cavities
• heart, lungs, stomach, and urinary bladder
12-5
Motor Divisions of PNS
• motor (efferent) division – carries signals from the CNS to
gland and muscle cells that carry out the body’s response
• effectors – cells and organs that respond to commands from the CNS
– somatic motor division – carries signals to skeletal muscles
• output produces muscular contraction as well as somatic reflexes –
involuntary muscle contractions
– visceral motor division (autonomic nervous system) - carries signals
to glands, cardiac muscle, and smooth muscle
• involuntary, and responses of this system and its receptors are visceral
reflexes
• sympathetic division
– tends to arouse body for action
– accelerating heart beat and respiration, while inhibiting digestive and urinary
systems
• parasympathetic division
– tends to have calming effect
– slows heart rate and breathing
– stimulates digestive and urinary systems
12-6
Subdivisions of Nervous System
12-7
Universal Properties of Neurons
• excitability (irritability)
– respond to environmental changes called stimuli
• conductivity
– neurons respond to stimuli by producing electrical
signals that are quickly conducted to other cells at
distant locations
• secretion
– when electrical signal reaches end of nerve fiber, a
chemical neurotransmitter is secreted that crosses
the gap and stimulates the next cell
12-8
Functional Types of Neurons
• sensory (afferent) neurons
– specialized to detect stimuli
– transmit information about them to the CNS
• begin in almost every organ in the body and end in CNS
• afferent – conducting signals toward CNS
• interneurons (association) neurons
– lie entirely within the CNS
– receive signals from many neurons and carry out the integrative function
• process, store, and retrieve information and ‘make decisions’ that determine
how the body will respond to stimuli
– 90% of all neurons are interneurons
– lie between, and interconnect the incoming sensory pathways, and the
outgoing motor pathways of the CNS
• motor (efferent) neuron
– send signals out to muscles and gland cells (the effectors)
• motor because most of them lead to muscles
• efferent neurons conduct signals away from the CNS
12-9
Fundamental Types of Neurons
12-10
Structure of a Neuron
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
• soma – the control center of the neuron
– also called neurosoma, cell body, or perikaryon
– has a single, centrally located nucleus with large
nucleolus
– cytoplasm contains mitochondria, lysosomes, a
Golgi complex, numerous inclusions, and
extensive rough endoplasmic reticulum and
cytoskeleton
– cytoskeleton consists of dense mesh of
microtubules and neurofibrils (bundles of actin
filaments)
• compartmentalizes rough ER into dark staining
Nissl bodies
– no centrioles – no further cell division
– inclusions – glycogen granules, lipid droplets,
melanin, and lipofuscin (golden brown pigment
produced when lysosomes digest worn-out
organelles)
• lipofuscin accumulates with age
• wear-and-tear granules
• most abundant in old neurons
12-11
Structure of a Neuron
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Dendrites
• dendrites – vast number
of branches coming from a
few thick branches from
the soma
Soma
Nucleus
Nucleolus
Trigger zone:
Axon hillock
Initial segment
– resemble bare branches of a tree
in winter
– primary site for receiving signals
from other neurons
– the more dendrites the neuron
has, the more information it can
receive and incorporate into
decision making
– provide precise pathway for the
reception and processing of
neural information
Axon collateral
Axon
Direction of
signal transmission
Internodes
Node of Ranvier
Myelin sheath
Schwann cell
Terminal
arborization
Figure 12.4a
Synaptic knobs
(a)
Figure 12.4a
12-12
Structure of a Neuron
• axon (nerve fiber) – originates from
a mound on one side of the soma
called the axon hillock
– cylindrical, relatively unbranched for most of
its length
• axon collaterals – branches of axon
– branch extensively on distal end
– specialized for rapid conduction of nerve
signals to points remote to the soma
– axoplasm – cytoplasm of axon
– axolemma – plasma membrane of axon
– only one axon per neuron
– Schwann cells and myelin sheath enclose
axon
– distal end, axon has terminal arborization –
extensive complex of fine branches
• synaptic knob (terminal button) – little swelling
that forms a junction (synapse) with the next
cell
• contains synaptic vesicles full of
neurotransmitter
(a)
Figure 12.4a
12-13
Variation in Neuron Structure
• multipolar neuron
– one axon and multiple dendrites
– most common
– most neurons in the brain and spinal
cord
• bipolar neuron
– one axon and one dendrite
– olfactory cells, retina, inner ear
• unipolar neuron
– single process leading away from the
soma
– sensory from skin and organs to
spinal cord
• anaxonic neuron
– many dendrites but no axon
– help in visual processes
Figure 12.5
12-14
Axonal Transport
• many proteins made in soma must be transported to axon
and axon terminal
– to repair axolemma, serve as gated ion channel proteins, as
enzymes or neurotransmitters
• axonal transport – two-way passage of proteins,
organelles, and other material along an axon
– anterograde transport – movement down the axon away from
soma
– retrograde transport – movement up the axon toward the soma
• microtubules guide materials along axon
– motor proteins (kinesin and dynein) carry materials “on their backs”
while they “crawl” along microtubules
• kinesin – motor proteins in anterograde transport
• dynein – motor proteins in retrograde transport
12-15
Two Types of Axonal Transport
Fast and Slow
• fast axonal transport – occurs at a rate of 20 – 400
mm/day
– fast anterograde transport (up to 400 mm/day)
• organelles, enzymes, synaptic vesicles and small molecules
– fast retrograde transport
• for recycled materials and pathogens - rabies, herpes simplex, tetanus,
polio viruses
– delay between infection and symptoms is time needed for transport up the
axon
• slow axonal transport or axoplasmic flow - 0.5 to 10
mm/day
– always anterograde
– moves enzymes, cytoskeletal components, and new axoplasm down
the axon during repair and regeneration of damaged axons
– damaged nerve fibers regenerate at a speed governed by slow
12-16
axonal transport
Neuroglial Cells
• about a trillion (1012) neurons in the nervous
system
• neuroglia outnumber the neurons by as much
as 50 to 1
• neuroglia or glial cells
– support and protect the neurons
– bind neurons together and form framework for
nervous tissue
– in fetus, guide migrating neurons to their destination
– if mature neuron is not in synaptic contact with
another neuron is covered by glial cells
• prevents neurons from touching each other
• gives precision to conduction pathways
12-17
Six Types of Neuroglial Cells
• four types occur only in CNS
– oligodendrocytes
• form myelin sheaths in CNS
• each arm-like process wraps around a nerve fiber forming an
insulating layer that speeds up signal conduction
– ependymal cells
• lines internal cavities of the brain
• cuboidal epithelium with cilia on apical surface
• secretes and circulates cerebrospinal fluid (CSF)
12-18
– microglia
• small, wandering macrophages formed white blood cell called
monocytes
• thought to perform a complete checkup on the brain tissue several
times a day
• wander in search of cellular debris to phagocytize
– astrocytes
• most abundant glial cell in CNS
• cover entire brain surface and most nonsynaptic regions of the
neurons in the gray matter of the CNS
• diverse functions
– form a supportive framework of nervous tissue
– have extensions (perivascular feet) that contact blood capillaries that stimulate
them to form a tight seal called the blood-brain barrier
– convert blood glucose to lactate and supply this to the neurons for nourishment
– Secrete nerve growth factors, promote neuron growth and synapse formation
– regulate chemical composition of tissue fluid by absorbing excess
neurotransmitters and ions
– astrocytosis or sclerosis – when neuron is damaged, astrocytes form hardened
12-19
scar tissue and fill space formerly occupied by the neuron
• two types occur only in PNS
– Schwann cells
• envelope nerve fibers in PNS
• wind repeatedly around a nerve fiber
• produces a myelin sheath similar to the ones produced by oligodendrocytes
in CNS
• assist in the regeneration of damaged fibers
– satellite cells
• surround the neurosomas in ganglia of the PNS
• provide electrical insulation around the soma
• regulate the chemical environment of the neurons
12-20
Glial Cells and Brain Tumors
• tumors - masses of rapidly dividing cells
– mature neurons have little or no capacity for mitosis
and seldom form tumors
• brain tumors arise from:
– meninges (protective membranes of CNS)
– by metastasis from non-neuronal tumors in other
organs
– most come from glial cells that are mitotically active
throughout life
• gliomas grow rapidly and are highly malignant
– blood-brain barrier decreases effectiveness of
chemotherapy
– treatment consists of radiation or surgery
12-21
Myelin
• myelin sheath – an insulating layer around a
nerve fiber
– formed by oligodendrocytes in CNS and
Schwann cells in PNS
– consists of the plasma membrane of glial cells
• 20% protein and 80 % lipid
• myelination – production of the myelin sheath
–
–
–
–
begins the 14th week of fetal development
proceeds rapidly during infancy
completed in late adolescence
dietary fat is important to nervous system
development
12-22
Myelin
• in PNS, Schwann cell spirals repeatedly around a single
nerve fiber
– lays down as many as a hundred layers of its own membrane
– no cytoplasm between the membranes
– neurilemma – thick outermost coil of myelin sheath
• contains nucleus and most of its cytoplasm
• external to neurilemma is basal lamina and a thin layer of fibrous
connective tissue – endoneurium
• in CNS – oligodendrocytes reaches out to myelinate
several nerve fibers in its immediate vicinity
– anchored to multiple nerve fibers
– cannot migrate around any one of them like Schwann cells
– must push newer layers of myelin under the older ones
• so myelination spirals inward toward nerve fiber
– nerve fibers in CNS have no neurilemma or endoneurium
12-23
Myelin
• many Schwann cells or oligodendrocytes
are needed to cover one nerve fiber
• myelin sheath is segmented
– nodes of Ranvier – gap between segments
– internodes – myelin covered segments from
one gap to the next
– initial segment – short section of nerve fiber
between the axon hillock and the first glial cell
– trigger zone
– the axon hillock and the initial segment
• play an important role in initiating a nerve
signal
12-24
Myelination in CNS
Myelin Sheath in PNS
Myelin
Figure 12.7b
Nerve fiber
(b)
nodes of Ranvier and internodes
12-25
Myelination in PNS
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Schwann cell
Axon
Basal lamina
Endoneurium
Nucleus
(a)
Neurilemma
Myelin sheath
Figure 12.7a
12-26
Diseases of Myelin Sheath
• degenerative disorders of the myelin sheath
– multiple sclerosis
• oligodendrocytes and myelin sheaths in the CNS deteriorate
• myelin replaced by hardened scar tissue
• nerve conduction disrupted (double vision, tremors, numbness, speech
defects)
• onset between 20 and 40 and fatal from 25 to 30 years after diagnosis
• cause may be autoimmune triggered by virus
– Tay-Sachs disease - a hereditary disorder of infants of Eastern
European Jewish ancestry
• abnormal accumulation of glycolipid called GM2 in the myelin sheath
–
–
–
–
normally decomposed by lysosomal enzyme
enzyme missing in individuals homozygous for Tay-Sachs allele
accumulation of ganglioside (GM2) disrupts conduction of nerve signals
blindness, loss of coordination, and dementia
• fatal before age 4
12-27
Unmyelinated Axons of PNS
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Neurilemma
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Myelin sheath
Unmyelinated
nerve fibers
Myelinated
axon
Schwann
cell cytoplasm
Basal
lamina
Neurilemma
Unmyelinated
axon
(c)
3µm
Schwann cell
© The McGraw-Hill Companies, Inc./Dr. Dennis Emery, Dept. of Zoology and Genetics, Iowa
State University, photographer
Figure 12.7c
Basal lamina
Figure 12.8
• Schwann cells hold 1 – 12 small nerve fibers in grooves on its surface
• membrane folds once around each fiber overlapping itself along the
edges
12-28
• mesaxon – neurilemma wrapping of unmyelinated nerve fibers
Conduction Speed of Nerve Fibers
• speed at which a nerve signal travels along a nerve fiber
depends on two factors
– diameter of fiber
– presence or absence of myelin
• signal conduction occurs along the surface of a fiber
– larger fibers have more surface area and conduct signals more
rapidly
– myelin further speeds signal conduction
• conduction speed
–
–
–
–
small, unmyelinated fibers - 0.5 - 2.0 m/sec
small, myelinated fibers 3 - 15.0 m/sec
large, myelinated fibers - up to 120 m/sec
slow signals supply the stomach and dilate pupil where speed is
less of an issue
– fast signals supply skeletal muscles and transport sensory
signals for vision and balance
12-29
Regeneration of Peripheral Nerves
• regeneration of a damaged peripheral nerve fiber can occur if:
– its soma is intact
– at least some neurilemma remains
• fiber distal to the injury cannot survive and degenerates
– macrophages clean up tissue debris at the point of injury and beyond
• soma swells, ER breaks up, and nucleus moves off center
– due to loss of nerve growth factor from neuron’s target cell
• axon stump sprouts multiple growth processes
– severed distal end continues to degenerate
• regeneration tube – formed by Schwann cells, basal lamina, and the
neurilemma near the injury
– regeneration tube guides the growing sprout back to the original target cells and
reestablishes synaptic contact
• nucleus returns to normal shape
12-30
• regeneration of damaged nerve fibers in the CNS cannot occur at all
Regeneration of Nerve Fiber
12-31
denervation atrophy of muscle due to loss of nerve contact by damaged nerve
Electrophysiology of Neurons
• Galen thought that the brain pumped a vapor called psychic pneuma
through hollow nerves and squirted in to the muscles to make them
contract
• Rene’ Descartes in the 17th century supported this theory
• Luigi Galvani discovered the role of electricity in muscle contraction in
the 18th century
• Camillo Golgi developed important method for staining neurons with
silver in the 19th century
• Santiago Ramon y Cajal set forth the neuron doctrine – nervous
pathway is not a continuous ‘wire’ or tube, but a series of cells
separated by gaps called synapses.
• neuron doctrine brought up two key questions:
– how does a neuron generate a electrical signal?
– how does it transmit a meaningful message to the next cell?
12-32
Nerve Growth Factor
• nerve growth factor (NGF) – a protein
secreted by a gland, muscle, and glial cells and
picked up by the axon terminals of the neurons.
– prevents apoptosis (programmed cell death) in
growing neurons
– enables growing neurons to make contact with their
target cells
• isolated by Rita Levi-Montalcini in 1950s
• won Nobel prize in 1986 with Stanley Cohen
• use of growth factors is now a vibrant field of
research
12-33
Electrical Potentials and Currents
• electrophysiology – cellular mechanisms for producing electrical
potentials and currents
– basis for neural communication and muscle contraction
• electrical potential – a difference in the concentration of charged
particles between one point and another
• electrical current – a flow of charged particles from one point to another
– in the body, currents are movement of ions, such as Na+ or K+ through gated
channels in the plasma membrane
– gated channels are opened or closed by various stimuli
– enables cell to turn electrical currents on and off
• living cells are polarized
• resting membrane potential (RMP) – charge difference across the plasma
membrane
– -70 mV in a resting, unstimulated neuron
– negative value means there are more negatively charged particles
the inside of the membrane than on the outside
on
12-34
Resting Membrane Potential
• RMP exists because of unequal electrolyte
distribution between extracellular fluid
(ECF) and intracellular fluid (ICF)
• RMP results from the combined effect of
three factors:
– ions diffuse down their concentration gradient
through the membrane
– plasma membrane is selectively permeable
and allows some ions to pass easier than
others
– electrical attraction of cations and anions to
each other
12-35
Creation of Resting Membrane Potential
• potassium ions (K+) have the greatest influence on RMP
– plasma membrane is more permeable to K+ than any other ion
– leaks out until electrical charge of cytoplasmic anions attracts it back in and
equilibrium is reached and net diffusion of K+ stops
– K+ is about 40 times as concentrated in the ICF as in the ECF
• cytoplasmic anions can not escape due to size or charge (phosphates,
sulfates, small organic acids, proteins, ATP, and RNA)
• membrane much less permeable to high concentration of sodium (Na+)
found outside the cell
– some leaks and diffuses into the cell down its concentration gradient
– Na+ is about 12 times as concentrated in the ECF as in the ICF
– resting membrane is much less permeable to Na+ than K+
• Na+/K+ pumps out 3 Na+ for every 2 K+ it brings in
– works continuously to compensate for Na+ and K+ leakage, and requires great
deal of ATP
• 70% of the energy requirement of the nervous system
– necessitates glucose and oxygen be supplied to nerve tissue (energy needed to
create the resting potential)
– pump contributes about -3 mV to the cell’s resting membrane
12-36
potential of -70 mV
Ionic Basis of Resting Membrane
Potential
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ECF
Na+ 145 mEq/L
K+
Na+
channel
K+
channel
4 mEq/L
Figure 12.11
Na+ 12 mEq/L
ICF
K+ 150 mEq/L
Large anions
that cannot
escape cell
• Na+ concentrated outside of cell (ECF)
• K+ concentrated inside cell (ICF)
12-37
Local Potentials
• local potentials - disturbances in membrane potential when a neuron is
stimulated
• neuron response begins at the dendrite, spreads through the soma,
travels down the axon, and ends at the synaptic knobs
• when neuron is stimulated by chemicals, light, heat or mechanical
disturbance
–
–
–
–
–
opens the Na+ gates and allows Na+ to rush in to the cell
Na+ inflow neutralizes some of the internal negative charge
voltage measured across the membrane drifts toward zero
depolarization - case in which membrane voltage shifts to a less negative value
Na+ diffuses for short distance on the inside of the plasma membrane producing
a current that travels towards the cell’s trigger zone – this short-range change in
voltage is called a local potential
12-38
Characteristics of Local Potentials
• differences of local potentials from action potentials
– are graded - vary in magnitude with stimulus strength
• stronger stimuli open more Na+ gates
– are decremental - get weaker the farther they spread
from the point of stimulation
• voltage shift caused by Na+ inflow diminishes rapidly with
distance
– are reversible - when stimulation ceases, K+ diffusion
out of cell returns the cell to its normal resting potential
– can be either excitatory or inhibitory - some
neurotransmitters (glycine) make the membrane potential
more negative – hyperpolarize it – becomes less
sensitive and less likely to produce an action potential
12-39
Excitation of a Neuron by a
Chemical Stimulus
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Dendrites
Soma Trigger
zone
Axon
Current
ECF
Ligand
Receptor
Plasma
membrane
of dendrite
Na+
ICF
Figure 12.12
12-40
Action Potentials
• action potential – more dramatic change produced by voltageregulated ion gates in the plasma membrane
– only occur where there is a high enough density of voltage-regulated
gates
– soma (50 -75 gates per m2 ) - cannot generate an action potential
– trigger zone (350 – 500 gates per m2 ) – where action potential is
generated
• if excitatory local potential spreads all the way to the trigger zone, and is still
strong enough when it arrives, it can open these gates and generate an
action potential
• action potential is a rapid up-and-down shift in the membrane
voltage
– sodium ions arrive at the axon hillock
– depolarize the membrane at that point
– threshold – critical voltage to which local potentials must rise to open
12-41
the voltage-regulated gates
• -55mV
Action Potentials
– when threshold is reached, neuron ‘fires’ and produces an action
potential
– more and more Na+ channels open in the trigger zone in a positive
feedback cycle creating a rapid rise in membrane voltage – spike
– when rising membrane potential passes 0 mV, Na+ gates are inactivated
• begin closing
• when all closed, the voltage peaks at +35 mV
• membrane now positive on the inside and negative on the outside
• polarity reversed from RMP
- depolarization
– by the time the voltage peaks, the slow
K+ gates are fully open
• K+ repelled by the positive
intracellular fluid now exit the cell
• their outflow repolarizes the
membrane
– shifts the voltage back to negative
numbers returning toward RMP
12-42
– K+ gates stay open longer than the Na+ gates
• slightly more K+ leaves the cell than Na+ entering
• drops the membrane voltage 1 or 2 mV more negative than the original RMP
– negative overshoot – hyperpolarization or afterpotential
– Na+ and K+ switch places across the membrane during an action potential
• only a thin layer of the cytoplasm next to the cell membrane is affected
• in reality, very few ions are involved
• action potential is often called a
spike – happens so fast
• characteristics of action potential versus a local potential
– follows an all-or-none law
• if threshold is reached, neuron fires at its maximum voltage
• if threshold is not reached it does not fire
– nondecremental - do not get weaker with distance
– irreversible - once started goes to completion and can not be stopped
12-43
Sodium and Potassium Gates
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
K+
Na+
K+
gate
1 Na+ and K+ gates closed
35
0
–70
Resting membrane
potential
mV
mV
Na+
gate
2 Na+ gates open, Na+
enters cell, K+ gates
beginning to open
35
0
–70
Depolarization begins
3 Na+ gates closed, K+ gates
fully open, K+ leaves cell
35
0
35
0
–70
Depolarization ends,
repolarization begins
4 Na+ gates closed,
K+ gates closing
mV
mV
Figure 12.14
–70
Repolarization complete
12-44
The Refractory Period
•
•
•
•
•
during an action potential and for a few
milliseconds after, it is difficult or impossible
to stimulate that region of a neuron to fire
again.
refractory period – the period of resistance
to stimulation
two phases of the refractory period
– absolute refractory period
• no stimulus of any strength will trigger
AP
• as long as Na+ gates are open
– relative refractory period
• only especially strong
stimulus will trigger new AP
– K+ gates are still open and any
affect of incoming Na+ is opposed
by the outgoing K+
refractory period is occurring only at a small
patch of the neuron’s membrane at one time
other parts of the neuron can be stimulated
while the small part is in refractory period
Figure 12.15
12-45
Signal Conduction in Unmyelinated
Fibers
• for communication to occur, the nerve signal must travel to
the end of the axon
• unmyelinated fiber has voltage-regulated ion gates along
its entire length
• action potential from the trigger zone causes Na+ to enter
the axon and diffuse into adjacent regions beneath the
membrane
• the depolarization excites voltage-regulated gates
immediately distal to the action potential.
• Na+ and K+ gates open and close producing a new action
potential
• by repetition the membrane distal to that is excited
• chain reaction continues to the end of the axon
12-46
Nerve Signal Conduction
Unmyelinated Fibers
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Dendrites
Cell body
Axon
Signal
Action potential
in progress
Refractory
membrane
Excitable
membrane
++++–––+++++++++++
––––+++–––––––––––
–––– +++–––––––––––
++++–––+++++++++++
+++++++++–––++++++
–––––––––+++––––––
–––––––––+++––––––
+++++++++–––++++++
+++++++++++++–––++
–––––––––––––+++––
–––––––––––––+++––
+++++++++++++–––++
Figure 12.16
12-47
Saltatory Conduction Myelinated Fibers
• voltage-gated channels needed for APs
– fewer than 25 per m2 in myelin-covered regions (internodes)
– up to 12,000 per m2 in nodes of Ranvier
• fast Na+ diffusion occurs between nodes
– signal weakens under myelin sheath, but still strong enough to stimulate an
action potential at next node
• saltatory conduction – the nerve signal seems to jump from node to node
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Figure 12.17a
(a)
Na+ inflow at node
generates action potential
(slow but nondecremental)
Na+ diffuses along inside
of axolemma to next node
(fast but decremental)
Excitation of voltageregulated gates will
generate next action
potential here
12-48
Saltatory Conduction
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
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(b)
Action potential
in progress
Refractory
membrane
Excitable
membrane
Figure 12.17b
• much faster than conduction in unmyelinated
fibers
12-49
Synapses
• a nerve signal can go no further when it reaches the end of the axon
– triggers the release of a neurotransmitter
– stimulates a new wave of electrical activity in the next cell across the
synapse
• synapse between two neurons
– 1st neuron in the signal path is the presynaptic neuron
• releases neurotransmitter
– 2nd neuron is postsynaptic neuron
• responds to neurotransmitter
• presynaptic neuron may synapse with a dendrite, soma, or axon of
postsynaptic neuron to form axodendritic, axosomatic or
axoaxonic synapses
• neuron can have an enormous number of synapses
– spinal motor neuron covered by about 10,000 synaptic knobs from other
neurons
• 8000 ending on its dendrites
• 2000 ending on its soma
• in cerebellum of brain, one neuron can have as many as 100,000
synapses
12-50
Synaptic Relationships Between
Neurons
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Soma
Synapse
Axon
Presynaptic
neuron
Direction of
signal
transmission
Postsynaptic
neuron
(a)
Axodendritic synapse
Axosomatic
synapse
(b)
Figure 12.18
Axoaxonic synapse
12-51
•
Discovery
of
Neurotransmitters
synaptic cleft -gap between neurons was discovered by Ramón y Cajal
through histological observations
• Otto Loewi, in 1921, demonstrated that neurons communicate by releasing
chemicals – chemical synapses
–
–
–
–
he flooded exposed hearts of two frogs with saline
stimulated vagus nerve of the first frog and the heart slowed
removed saline from that frog and found it slowed heart of second frog
named it Vagusstoffe (“vagus substance”)
•
later renamed acetylcholine, the first known neurotransmitter
• electrical synapses do exist
– some neurons, neuroglia, and cardiac and single-unit smooth muscle
– gap junctions join adjacent cells
• ions diffuse through the gap junctions from one cell to the next
– advantage of quick transmission
• no delay for release and binding of neurotransmitter
• cardiac and smooth muscle and some neurons
– disadvantage is they cannot integrate information and make decisions
• ability reserved for chemical synapses in which neurons communicate by releasing
12-52
neurotransmitters
Synaptic Knobs
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Axon of
presynaptic
neuron
Synaptic
knob
Soma of
postsynaptic
neuron
© Omikron/Science Source/Photo Researchers, Inc
Figure 12.19
12-53
Structure of a Chemicynapse
• synaptic knob of presynaptic neuron contains synaptic
vesicles containing neurotransmitter
– many docked on release sites on plasma membrane
• ready to release neurotransmitter on demand
– a reserve pool of synaptic vesicles located further away from
membrane
• postsynaptic neuron membrane contains proteins that
function as receptors and ligand-regulated ion gates
12-54
Structure of a Chemical Synapse
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Microtubules
of cytoskeleton
Axon of presynaptic neuron
Mitochondria
Postsynaptic neuron
Synaptic knob
Synaptic vesicles
containing neurotransmitter
Synaptic cleft
Neurotransmitter
receptor
Postsynaptic neuron
Neurotransmitter
release
Figure 12.20
• presynaptic neurons have synaptic vesicles with
neurotransmitter and postsynaptic have receptors and
ligand-regulated ion channels
12-55
Neurotransmitters and Related
Messengers
• more than 100 neurotransmitters have been identified
• fall into four major categories according to chemical
composition
– acetylcholine
• in a class by itself
• formed from acetic acid and choline
– amino acid neurotransmitters
• include glycine, glutamate, aspartate, and -aminobutyric acid (GABA)
– monoamines
• synthesized from amino acids by removal of the –COOH group
• retaining the –NH2 (amino) group
• major monoamines are:
– epinephrine, norepinephrine, dopamine (catecholamines)
– histamine and serotonin
– neuropeptides
12-56
Categories of Neurotransmitters
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Acetylcholine
CH3
O
+
H3C N CH2 CH2 O C CH3
CH3
Catecholamines
HO
OH
CH CH2 NH CH2
Amino acids
HO
HO
C CH2 CH2 CH2 NH2
Tyr
Enkephalin
Arg Pro Lys
OH
CH CH2 NH2
Norepinephrine
HO
HO
C CH2
HO
NH2
Glycine
O
O
C CH CH2 C
HO
OH
NH2
C
Dopamine
HO
O
OH
Glutamic acid
CH2 CH2 NH2
Ser
Thr Met Phe
Glu
Glu Phe
SO4
Gly
N
Substance P
Phe
Cholecystokinin
Tyr
ß-endorphin
Serotonin
Glu
N
Leu Met
Gly
Lys
Ser
N
Aspartic acid
C CH CH2 CH2
HO
NH2
CH2 CH2 NH2
HO
Pro
Glu
Phe Gly
Asp Tyr Met Gly Trp Met Asp
GABA
O
O
Met Phe
Gly Gly
Epinephrine
HO
O
Neuropeptides
Monoamines
CH2 CH2 NH2
Histamine
Thr
Ala
Pro
Asn
Lys
Leu
Val
Thr Leu
Phe
IIe
IIe
Lys Asn Ala Tyr
Lys
Lys
Gly
Glu
Figure 12.21
12-57
Neuropeptides
• chains of 2 to 40 amino acids
– beta-endorphin and substance P
• act at lower concentrations than
other neurotransmitters
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Neuropeptides
Met Phe
Gly Gly
Tyr
Enkephalin
Arg Pro Lys
Pro
Glu
Glu Phe
Phe Gly
Leu Met
Substance P
• longer lasting effects
• stored in axon terminal as larger
secretory granules (called
dense-core vesicles)
• some function as hormones or
neuromodulators
• some also released from
digestive tract
– gut-brain peptides cause food
cravings
Ser
Thr Met Phe
Glu
Asp Tyr Met Gly Trp Met Asp
SO4
Gly
Phe
Cholecystokinin
Gly
Tyr
Lys
ß-endorphin
Ser
Glu
Thr
Ala
Pro
Asn
Lys
Leu
Val
Thr Leu
Phe
IIe
IIe
Lys Asn Ala Tyr
Lys
Lys
Gly
Glu
Figure 12.21
12-58
Function of Neurotransmitters
at Synapse
• they are synthesized by the presynaptic
neuron
• they are released in response to
stimulation
• they bind to specific receptors on the
postsynaptic cell
• they alter the physiology of that cell
12-59
Effects of Neurotransmitters
• a given neurotransmitter does not have
the same effect everywhere in the body
• multiple receptor types exist for a
particular neurotransmitter
– 14 receptor types for serotonin
• receptor governs the effect the
neurotransmitter has on the target cell
12-60
Synaptic Transmission
• neurotransmitters are diverse in their action
– some excitatory
– some inhibitory
– some the effect depends on what kind of receptor the
postsynaptic cell has
– some open ligand-regulated ion gates
– some act through second-messenger systems
• three kinds of synapses with different modes of action
– excitatory cholinergic synapse
– inhibitory GABA-ergic synapse
– excitatory adrenergic synapse
• synaptic delay – time from the arrival of a signal at the
axon terminal of a presynaptic cell to the beginning of an
action potential in the postsynaptic cell
– 0.5 msec for all the complex sequence of events to occur
12-61
Excitatory Cholinergic Synapse
• cholinergic synapse – employs acetylcholine (ACh) as its
neurotransmitter
– ACh excites some postsynaptic cells
• skeletal muscle
– inhibits others
•
describing excitatory action
– nerve signal approaching the synapse, opens the voltage-regulated
calcium gates in synaptic knob
– Ca2+ enters the knob
– triggers exocytosis of synaptic vesicles releasing ACh
– empty vesicles drop back into the cytoplasm to be refilled with ACh
– reserve pool of synaptic vesicles move to the active sites and release
their ACh
– ACh diffuses across the synaptic cleft
– binds to ligand-regulated gates on the postsynaptic neuron
– gates open
– allowing Na+ to enter cell and K+ to leave
• pass in opposite directions through same gate
12-62
Excitatory Cholinergic Synapse
- as Na+ enters the cell it
spreads out along the inside of
the plasma membrane and
depolarizes it producing a local
potential called the
postsynaptic potential
- if it is strong enough and
persistent enough
- it opens voltage-regulated ion
gates in the trigger zone
causing the postsynaptic
neuron to fire
Figure 12.22
12-63
Inhibitory GABA-ergic Synapse
• GABA-ergic synapse employs -aminobutyric acid as its
neurotransmitter
• nerve signal triggers release of GABA into synaptic cleft
• GABA receptors are chloride channels
• Cl- enters cell and makes the inside more negative than
the resting membrane potential
• postsynaptic neuron is inhibited, and less likely to fire
12-64
Excitatory Adrenergic Synapse
• adrenergic synapse employs the neurotransmitter norepinephrine (NE)
also called noradrenaline
• NE and other monoamines, and neuropeptides acts through second
messenger systems such as cyclic AMP (cAMP)
• receptor is not an ion gate, but a transmembrane protein associated
with a G protein
–
–
–
–
–
unstimulated NE receptor is bound to a G protein
binding of NE to the receptor causes the G protein to dissociate from it
G protein binds to and activates adenylate cyclase enzyme
induces the conversion of ATP to cyclic AMP
cyclic AMP can induce several alternative effects in the cell
• causes the production of an internal chemical that binds to a ligandregulated ion gate from inside of the membrane, opening the gate and
depolarizing the cell
• can activate preexisting cytoplasmic enzymes that lead do diverse
metabolic changes
• can induce genetic transcription, so that the cell produces new
cytoplasmic enzymes that can lead to diverse metabolic effects
12-65
Excitatory Adrenergic Synapse
• slower to respond than cholinergic and GABA-ergic synapses
• has advantage of enzyme amplification – single molecule of NE
can produce vast numbers of product molecules in the cell
12-66
Figure 12.23
Cessation of the Signal
• mechanisms to turn off stimulation to keep postsynaptic neuron from
firing indefinitely
– neurotransmitter molecule binds to its receptor for only 1 msec or so
• then dissociates from it
– if presynaptic cell continues to release neurotransmitter
• one molecule is quickly replaced by another and the neuron is restimulated
• stop adding neurotransmitter and get rid of that which is already there
– stop signals in the presynaptic nerve fiber
– getting rid of neurotransmitter by:
• diffusion
– neurotransmitter escapes the synapse into the nearby ECF
– astrocytes in CNS absorb it and return it to neurons
• reuptake
– synaptic knob reabsorbs amino acids and monoamines by endocytosis
– break neurotransmitters down with monoamine oxidase (MAO) enzyme
– some antidepressant drugs work by inhibiting MAO
• degradation in the synaptic cleft
– enzyme acetylcholinesterase (AChE) in synaptic cleft degrades ACh
into acetate and choline
– choline reabsorbed by synaptic knob
12-67
Neuromodulators
• neuromodulators – hormones, neuropeptides, and other
messengers that modify synaptic transmission
– may stimulate a neuron to install more receptors in the postsynaptic
membrane adjusting its sensitivity to the neurotransmitter
– may alter the rate of neurotransmitter synthesis, release, reuptake, or
breakdown
• enkephalins – a neuromodulator family
– small peptides that inhibit spinal interneurons from transmitting pain
signals to the brain
• nitric oxide (NO) – simpler neuromodulator
– a lightweight gas release by the postsynaptic neurons in some areas of
the brain concerned with learning and memory
– diffuses into the presynaptic neuron
– stimulates it to release more neurotransmitter
– one neuron’s way of telling the other to ‘give me more’
– some chemical communication that goes backward across
12-68
the synapse
Neural Integration
• synaptic delay slows the transmission of nerve signals
• more synapses in a neural pathway, the longer it takes for
information to get from its origin to its destination
– synapses are not due to limitation of nerve fiber length
– gap junctions allow some cells to communicate more rapidly than
chemical synapses
• then why do we have synapses?
– to process information, store it, and make decisions
– chemical synapses are the decision making devises of the nervous
system
– the more synapses a neuron has, the greater its informationprocessing capabilities.
– pyramidal cells in cerebral cortex have about 40,000 synaptic
contacts with other neurons
– cerebral cortex (main information-processing tissue of your brain)
has an estimated 100 trillion (1014) synapses
• neural integration – the ability of your neurons to process
12-69
information, store and recall it, and make decisions
Postsynaptic Potentials - PSP
• neural integration is based on the postsynaptic
potentials produced by neurotransmitters
• typical neuron has a resting membrane potential
of -70 mV and threshold of about -55 mV
• excitatory postsynaptic potentials (EPSP)
– any voltage change in the direction of threshold that
makes a neuron more likely to fire
• usually results from Na+ flowing into the cell cancelling some
of the negative charge on the inside of the membrane
– glutamate and aspartate are excitatory brain
neurotransmitters that produce EPSPs
12-70
Postsynaptic Potentials - PSP
• inhibitory postsynaptic potentials (IPSP)
– any voltage change away from threshold that makes a
neuron less likely to fire
• neurotransmitter hyperpolarizes the postsynaptic cell and makes it
more negative than the RMP making it less likely to fire
• produced by neurotransmitters that open ligand-regulated chloride
gates
– causing inflow of Cl- making the cytosol more negative
– glycine and GABA produce IPSPs and are inhibitory
– acetylcholine (ACh) and norepinephrine are excitatory
to some cells and inhibitory to others
• depending on the type of receptors on the target cell
• ACh excites skeletal muscle, but inhibits cardiac muscle
due to the different type of receptors
12-71
Postsynaptic Potentials
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
0
mV
–20
–40
Threshold
–60
Repolarization
–80
(a)
Resting membrane
potential
EPSP
Depolarization
Stimulus
Time
0
mV
–20
–40
Threshold
–60
IPSP
Resting membrane
potential
Figure 12.24
–80
Hyperpolarization
(b)
Stimulus
Time
12-72
Summation, Facilitation, and Inhibition
• one neuron can receive input from thousands of other neurons
• some incoming nerve fibers may produce EPSPs while others produce
IPSPs
• neuron’s response depends on whether the net input is excitatory or
inhibitory
• summation – the process of adding up postsynaptic potentials and
responding to their net effect
– occurs in the trigger zone
• the balance between EPSPs and IPSPs enables the nervous system to
make decisions
• temporal summation – occurs when a single synapse generates EPSPs so
quickly that each is generated before the previous one fades
– allows EPSPs to add up over time to a threshold voltage that triggers an action
potential
• spatial summation – occurs when EPSPs from several different synapses
add up to threshold at an axon hillock.
– several synapses admit enough Na+ to reach threshold
– presynaptic neurons cooperate to induce the postsynaptic neuron to fire
12-73
Temporal and Spatial Summation
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
3 Postsynaptic
neuron fires
1 Intense stimulation
by one presynaptic
neuron
2 EPSPs spread
from one synapse
to trigger zone
(a) Temporal summation
3 Postsynaptic
neuron fires
2 EPSPs spread from
several synapses
1 Simultaneous stimulation to trigger zone
by several presynaptic
neurons
(b) Spatial summation
Figure 12.25
12-74
Summation of EPSPs
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
+40
+20
0
mV
Action potential
–20
–40
–60
–80
Threshold
EPSPs
Resting
membrane
potential
Stimuli
Figure 12.26
Time
• does this represent spatial or temporal summation?
12-75
Summation, Facilitation, and Inhibition
•
neurons routinely work in groups to modify each other’s action
•
facilitation – a process in which one neuron enhances the effect of another one
– combined effort of several neurons facilitates firing of postsynaptic neuron
•
presynaptic inhibition – process in which one presynaptic neuron suppresses
another one
– the opposite of facilitation
– reduces or halts unwanted synaptic transmission
– neuron I releases inhibitory GABA
• prevents voltage-gated calcium channels from opening in synaptic knob and
presynaptic neuron releases less or no neurotransmitter
Figure 12.27
12-76
Neural Coding
• neural coding – the way in which the nervous system
converts information to a meaningful pattern of action
potentials
• qualitative information depends upon which neurons fire
– labeled line code – each nerve fiber to the brain leads from a receptor
that specifically recognizes a particular stimulus type
• quantitative information – information about the intensity of a
stimulus is encoded in two ways:
– one depends on the fact that different neurons have different thresholds
of excitation
• stronger stimuli causes a more rapid firing rate
• excitement of sensitive, low threshold fibers gives way to excitement of less
sensitive, high-threshold fibers as intensity of stimuli increases
– other way depends on the fact that the more strongly a neuron is
stimulated, the more frequently it fires
• CNS can judge stimulus strength from the firing frequency of afferent
neurons
12-77
Neural Coding
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Action potentials
2g
5g
10 g
20 g
Time
Figure 12.28
12-78
Neural Pools and Circuits
•
neural pools – neurons function in large groups, each of which consists of millions of
interneurons concerned with a particular body function
– control rhythm of breathing
– moving limbs rhythmically when walking
•
information arrives at a neural pool through one or more input neurons
– branch repeatedly and synapse with numerous interneurons in the pool
– some input neurons form multiple synapses with a single postsynaptic cell
• can produce EPSPs in all points of contact with that cell
• through spatial summation, make it fire more easily than if they synapsed with it at only
one point
– within the discharge zone of an input neuron
• that neuron acting alone can make the postsynaptic cells fire
– in a broader facilitated zone, it synapses with still other neurons in the pool
• fewer synapses on each of them
• can only stimulate those neurons to fire only with the assistance of other input neurons
Figure 12.29
12-79
Kinds of Neural Circuits
• diverging circuit
– one nerve fiber branches and synapses with several postsynaptic cells
– one neuron may produce output through hundreds of neurons
• converging circuit
– input from many different nerve fibers can be funneled to one neuron or
neural pool
– opposite of diverging circuit
• reverberating circuits
– neurons stimulate each other in linear sequence but one cell restimulates
the first cell to start the process all over
– diaphragm and intercostal muscles
• parallel after-discharge circuits
– input neuron diverges to stimulate several chains of neurons
• each chain has a different number of synapses
• eventually they all reconverge on a single output neuron
• after-discharge – continued firing after the stimulus stops
12-80
Neural Circuits
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Diverging
Converging
Input
Output
Output
Input
Reverberating
Parallel after-discharge
Figure 12.30
Input
Input
Output
Output
12-81
Memory and Synaptic Plasticity
• physical basis of memory is a pathway through
the brain called a memory trace or engram
– along this pathway, new synapses were created or
existing synapses modified to make transmission
easier
– synaptic plasticity – the ability of synapses to
change
– synaptic potentiation - the process of making
transmission easier
• kinds of memory
– immediate, short- and long-term memory
– correlate with different modes of synaptic potentiation
12-82
Immediate Memory
• immediate memory – the ability to hold
something in your thoughts for just a few
seconds
– essential for reading ability
• feel for the flow of events (sense of the
present)
• our memory of what just happened
“echoes” in our minds for a few seconds
– reverberating circuits
12-83
Short-Term or Working Memory
• short-term memory (STM) - lasts from a few
seconds to several hours
– quickly forgotten if distracted
– calling a phone number we just looked up
– reverberating circuits
• facilitation causes memory to last longer
– tetanic stimulation – rapid arrival of repetitive signals
at a synapse
• causes Ca2+ accumulation and postsynaptic cell more likely to
fire
– post-tetanic potentiation - to jog a memory
• Ca2+ level in synaptic knob stays elevated
• little stimulation needed to recover memory
12-84
Long-Term Memory
• types of long-term memory
– declarative - retention of events that you can put into
words
– procedural - retention of motor skills
• physical remodeling of synapses
– new branching of axons or dendrites
• molecular changes - long-term potentiation
– changes in receptors and other features increases
transmission across “experienced” synapses
– effect is longer-lasting
12-85
Molecular Changes and
Long-Term Memory
• molecular changes are called long-term
potentiation
• method described
– receptors on synaptic knobs are usually blocked by
Mg+2 ions
– when bind glutamate and receive tetanic stimuli, they
repel Mg+2 and admit Ca+2 into the dendrite – Ca+2
acts as second messenger
• more synaptic knob receptors are produced
• synthesizes proteins involved n synapse remodeling
• releases nitric oxide that triggers more neurotransmitter
release at presynaptic neuron
12-86
Alzheimer Disease
• 100,000 deaths/year
– 11% of population over 65; 47% by age 85
• memory loss for recent events, moody, combative, lose ability to
talk, walk, and eat
• show deficiencies of acetylcholine (ACh) and nerve growth factor
(NGF)
• diagnosis confirmed at autopsy
– atrophy of gyri (folds) in cerebral cortex
– neurofibrillary tangles and senile plaques
– formation of beta-amyloid protein from breakdown product of plasma
membranes
• genetics implicated
• treatment - halt beta-amyloid production
– research halted due to serious side effects
– Give NGF or cholinesterase inhibitors
12-87
Alzheimer Disease Effects
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Neurons with
neurofibrillary
tangles
Shrunken
gyri
Wide sulci
Senile plaque
(b)
(a)
© Simon Fraser/Photo Researchers, Inc.
Custom Medical Stock Photo, Inc.
Figure 12.31a
Figure 12.31b
12-88
Parkinson Disease
• progressive loss of motor function beginning in 50’s or 60’s no recovery
– degeneration of dopamine-releasing neurons
• dopamine normally prevents excessive activity in motor centers (basal
nuclei)
• involuntary muscle contractions
– pill-rolling motion, facial rigidity, slurred speech,
– illegible handwriting, slow gait
• treatment - drugs and physical therapy
– dopamine precursor (L-dopa) crosses brain barrier – bad side effects
on heart & liver
– MAO inhibitor slows neural degeneration
– surgical technique to relieve tremors
12-89