Nerves
BIEN 500
Steven A. Jones
Divisions of the Nervous System
• Higher brain/cortical level
– Memory storehouse
– Thought
– Control of other parts of the nervous system
• Subconscious activities
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–
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Medulla
Control of respiration & arterial pressure
Pons
Mesencephalon
Hypothalamus
Thalamus
Cerebellum
Basal ganglia
Emotion
• Spinal Cord
– Reflex activities (walking, withdrawal from pain, leg support,
control of blood flow
Neuron Anatomy
Signals from dendrites can
be transmitted either to
knobs on the cell body or
knobs on the dendrites
Brain
Cell
Body
Dendrites
Axon
Conduction generally
occurs in one direction.
Spinal
Cord
Signals
• Nerves deliver sequences of spikes.
• Spike frequency translates to signal
strength.
Time
Signals
Frequency of discharge (s-1)
• Response threshold and maximum spike
frequency depend on nerve type.
600
500
Neuron 1
3
400
300
200
2
100
Excitatory State
Note: Threshold
for Neuron 3 has a
higher threshold,
but ultimately has
higher frequency of
discharge.
Fatigue
• Nerve is incapable of producing more
action potentials
• Causes are:
– Depletion of transmitter substances in the
presynaptic terminals
– Inactivation of postsynaptic membrane
receptors
– Buildup of abnormal amounts of ions at the
postsynaptic cell
Other Effects
• Post-tetanic facilitation – nerve becomes
more excitable after resting from intense
stimulation.
• pH
– Alkalosis causes higher excitability
– Acidosis causes lower excitability
• Hypoxia – reduces excitability
Drugs
Increases Excitability Caffeine, theophylline,
(Reduced Threshold) theobromide (coffee, tea
and cocoa, respectively)
Decrease Inhibition
Strichnine – can cause
muscle spasms
Increase membrane Most anesthetics
threshold
Connections
• Synaptic cleft (2-3 nm wide)
• Presynaptic Terminal has
– Mitochondria
– Neural Transmitter Vesicles
• Postsynaptic Terminal (cell soma) has:
– Receptor Proteins
Mitochondria
Transmitter
Vesicles
Soma
Receptor
Proteins
Causes of Synaptic Delay
1. Discharge of neural transmitter.
2. Diffusion of the transmitter across
the cleft.
3. Response of membrane receptor to
the neural transmitter.
4. Action of the receptor to increase
membrane permeability.
5. Inward diffusion of sodium.
Discharge
Na+
Receptor Response
Diffusion
Receptor Effect
Release of Neural Transmitter
• Voltage gated Ca++ channels release Ca++
• Ca++ causes release of neural transmitter.
• Each vesicle secretes transmitter by
pinocytosis.
• Transmitter Acetylcholine
– 2000-10000 molecules per vesicle
– Enough vesicles for 10,000 action potentials
Ion Receptor Responses
• Cation Channels
– Short term, excitatory
– Allow passage of cations (Mostly Na+, but also
K+, Ca++)
• Anion Channels
– Short term, inhibitory
– Allow passage of anions (Mainly Cl-, inhibitory
hyperpolarization)
G Protein Receptors
Extracellular
Transmitter Substance


Intracellular


 Portion affects the neuron (e.g. opening
potassium channel, transcription, enzyme
activation)
Second Messenger Receptor
Responses
• Long-term responses.
• G Protein Channels have ,  and  components.
•  component is released, possibly causing:
– Opening of an ion channel
– Activation of cyclic Adenosine Monophosphate (cAMP)
• Can alter cell structure and excitability.
– Activation of intracellular enzymes
– Activation of gene transcription
• Formation of new proteins.
• Change in metabolic machinery
• Can be important in memory
Action Potential
0
Potential
Inside (mV)
-70
Time (ms)
Excessive K+
Inside
Influx of
Na+
Outflux of
Na+, Influx
of K+
Mechanisms of Excitation
• Opening of sodium channels
– Makes inside potential less negative
• Depressed chloride or potassium channel
conduction
• Metabolic changes
– Direct impact
– Increase in the number of excitatory receptors
– Decrease in the number of inhibitory
receptors.
Mechanisms of Inhibition
• Opening of chloride channels
– makes inside more negative
• Increasing K+ Conductance (K+ diffuses out)
• Activation of inhibiting receptor enzymes
Neural Transmitters
• Approximately 50 neural transmitters are
known.
• Small molecules
– Fast-acting
– Acute responses
• Large polypeptides
– Slow-acting
– Long-term responses
Neural Transmitters
• Factors in response
– Amount of transmitter generated
– Number of receptors
– Transmitter uptake mechanisms
– Transmitter inactivation
– Receptor inactivation
Small Molecule Neural Transmitters
Class I: Acetylcholine Class III: Amino Acids
Class II: The Amines
-Aminobutyric acid (GABA)
Norepinephrine
Glycine
Epinephrine
Glutamate
Dopamine
Aspartate
Serotonin Class IV:
Histamine
Nitric Oxide
Recycling of Transmitter Vesicles
Recycling of Transmitter Vesicles
Concentrating
Proteins
Recycling of Transmitter Vesicles
Concentrating
Proteins
Recycling of Transmitter Vesicles
Small Neural Transmitters
Acetylcholine:
Norepinephrine:
Glutamate:
Dopamine:
Glycine:
Excitation (mostly)
Excitation (mostly)
Excitation
Inhibition
Inhibition
GABA: Inhibition
Serotonin: Pain inhibition, Sleep
Nitric Oxide Memory, Smooth muscle relaxation,
(NO): inhibits platelets and cellular
proliferation. NO is not stored.
Selected Neuropeptides
• Hypothalamic
– Leuteinizing hormone
• Pituitary
– Growth Hormone
– Vasopressin
– Oxytocin
• Acting on Gut and Brain
– Insulin
– Glucagon
• Others
– Angiotensin II
– Bradykinin
– Sleep Peptides
Neuropeptides
• Usually one type per neuron.
• Must be removed
– By diffusion from synaptic cleft
– By enzymatic destruction
– By active transport into presynaptic terminal (recycling)
•
•
•
•
•
•
Synthesized in cell body.
More “expensive” to generate.
Transmitted to synapse by streaming.
Vesicles are not reused.
More potent than small neural transmitters
More prolonged action.
Response Time for Neural
Transmitter
 L D
2
L  gap width
D  Diffusion Coefficient
If L is 3 nm and D is 3.45 x 10-6 cm2/s (D for serotonin), then:
  3  10 cm / 3.45  10 6 cm2 s  0.87  10 8 s
7
2
It follows that the transport of the neural transmitter
across the synaptic cleft is not the time limiting factor in
neural transmission.
Other Factors in Response Time
• Release of transmitter.
• Response time of receptors.
• Response time for action after receptor
response.
Connections
• Facilitated (subthreshold or subliminal) Zone
• Discharge Zone
– Transmitting nerve will trigger receiving nerve
Facilitated
Discharge
Connections
• Inhibition Zone
– Exists when dendrites are inhibitory instead of
excitatory.
Inhibition Zone
(entire field of inhibiting
neuron)
Simultaneous Excitation and
Inhibition
• Different neural transmitters for excitation
and inhibition.
• Intervening Inhibitory synapse
• Might be used to control opposing muscles
Excitatory Synapse
Excitation
Inhibition
Inhibitory Synapse
Divergence
• To increase the intensity
on a given element:
• To cause the same
effect on different
elements:
Afterdischarge
• Response lasts longer than input
• Reverberatory (positive feedback-fig 46-13)
• Can add facilitation and inhibition (like FET?)
Without Afterdischarge
Potential
Inside (mV)
With Afterdischarge
Time (ms)
Time
Afterdischarge
Simplest case – neuronal signal feeds back on
itself, causing re-triggering.
Afterdischarge with
Facilitation/Inhibition
External Neuron
External neuron excites or inhibits the feedback
connection.
Circuit Analogue to Oscillatory Pool
Schmitt Trigger (has
hysteresis, positive
feedback)
Saturation
Voltage (V)
+
-
Voltage (V)
R1
+
Time (s)
Integrator
Substitute FET transistor for R1 to get voltage
(signal) controlled oscillator.
Time (s)
Continuous Neural Signals
• Intrinsic Neuronal Excitability
• Reverberatig Circuits
– Can be controlled by facilitation/inhibition
– Dog scratching, breathing
– Uncontrolled – epilepsy
– Inhibition mechanisms
• Inhibitory feedback
• Synaptic fatigue
Memory
• Mostly occurs in the cerebral cortex
• May also occur in basal sections of brain &
spinal cord.
• Facilitation – The more often a synapse
fires, the easier it is to fire again.
• Pathways can fire without the initial
stimulus.
Ch. 47: Somatic Sensations
• Categories of somatic senses
– Mechanireceptive somatic sensors
• Tactile
• Position
– Thermoreceptive senses
– Pain sense
• Position senses
– Rate of movement
– Static position
• Tactile senses
• Touch, pressure, vibration, tickle.
Tickle and Itch
• Receptors are almost exclusively in the
superficial layers of the skin
• Transmitted by small, type C,
unmyelinated fibers (similar to slow,
aching pain).
• Useful in detecting fleas, flies, etc.
• Pain inhibits itch by lateral inhibition
Somatic Sensory Pathways
• Dorsal Column
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Touch signals for localization
Touch sensations for fine intensity
Phasic (e.g. vibratory) sensations
Position Sensations
Fine Pressure
• Anterolateral System
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Pain
Warm and Cold
Crude touch and pressure
Tickle and Itch
Sexual Sensations
Somatic Sensation II, Pain,
Headache, and Thermal Sensations
• Fast Pain
– Sharp/pricking/acute/electric pain
– As when stuck by a needle or electric shock
• Slow Pain
– Types of slow pain
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•
•
•
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Slow burning pain
Aching pain
Throbbing pain
Nauseous pain
Chronic pain
– Usually indicates tissue destruction
Purpose of Pain
Patient: “Doctor, it hurts when I do this.”
Doctor: “Well, don’t do that!”
Pain Receptors
• All pain receptors are free nerve endings.
• Pain receptors are found in:
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Superficial skin layers
Periosteum
Arterial walls
Joint surfaces
Falx and tentorium of cranial vault
Other areas are sparsely populated
• Any widespread tissue damage can cause slow,
chronic aching pain.
Types of Pain Stimuli
• Mechanical
• Thermal
• Chemical
– Caused by bradykinin, serogonin, histamine,
K+, acetylcholine, proteolytic enzymes
– Enhanced by prostaglandins, substance P.
Causes of Pain
• Rate of tissue damage
– Pain is felt at about 45 degrees.
– This is the temp at which tissue becomes
damaged.
• Extracts from damaged tissue will induce
pain.
• Ischemia (possibly because of lactic acid)
Pain Fibers
• Fast pain
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Transmitted by type A fibers (6 to 30 m/s)
Probably transmitted by glutamate
Tells you to take immediate action (take hand off of burner)
Highly localized
Passes through neospinothalamic tract
• Slow, chronic pain
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Transmitted by type C fibers (0.5 to 5 m/s)
Probably transmitted by Substance P
Becomes more painful over time
Reminds you that you did something stupid
Poorly localized
Transmitted through paleospinothalamic pathways
Analgesia System
• Stimulation of the periaqueductal gray area or
the raphe magnus nucleus can suppress
strong pain from the dorsal spinal roots.
• Enkephalins and serotonin (neurotransmitters) are involved.
• Opiate system – Endorphins and Enkephalins
• Inhibition by tactile sensory signals
– E.g. rubbing the skin
Referred Pain
• Classic example is heart attack
– Pain may be felt in arm, or masked as
indigestion.
• Pain receptors follow pathways to other
areas of the body (cross-wiring).
Visceral Pain
• Gut Pain – not so much acute, but highly
sensitive to diffuse pain.
• Some viscera do not feel pain
– Parenchyma of the liver
– Alveoli of the lungs
• Causes are
– Ischemia
– Chemical stimuli
– Spasm (e.g. of ball bladder, bile duct, ureter)
Abnormal Pain
• Hyperalgesia (excitable pain pathway)
– Excessive sensitivity of pain receptors (e.g.
sunburned skin)
– Facilitation of sensory transmission
• Thalamic syndrome
• Herpes Zoster (Shingles)
– Herpes virus infects dorsal ganglia
– Also causes skin rash
• Tic Douloureux
– Felt in one side of the face
– Feels like electric shock
Headache
• Brain is insensitive to pain
• Regions around the brain are sensitive
– Meninges
– Nasal Sinuses
– Venous sinuses
– Tentorium
– Dura
Types of Headache
• Migrane
– Cause is not well understood
– May result from vessel spasm – vessel expands after the vessel is
exhausted.
• Meningitis
– Infection of meninges
– West Nile virus
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•
•
•
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Low cerebral spinal fluid (brain impinges on dural surfaces)
Alcoholic Headache (“don’t drink that poision!)
Constipation headache (occurs even if spinal cord is cut).
Muscle spasm headache (muscles attached to scalp & neck)
Sinus Headache (inflammation, pressure)
Thermal Sensations
Impulses per Second
Cold Pain
Warmth
Receptors
Heat Pain
Cold Receptors
5
45
25
Temperature (ºC)
60
Thermal Sensation
• If temperature is too cold, subject stops
feeling pain.
• Cold pain and hot pain feel similar.
• Receptors are more sensitive to rates of
change of temperature, rather than
temperature itself.
– Pool water seems colder when you first get in.
– Nerves adapt to the cooler temperature.
– Eventually loss of heat will cause shivering.