1. Nerves
BIEN 500
Steven A. Jones

2. Divisions of the Nervous System
Higher brain/cortical level
Memory storehouse
Thought
Control of other parts of the nervous system
Subconscious activities
Medulla
Pons
Mesencephalon
Hypothalamus
Thalamus
Cerebellum
Basal ganglia
Spinal Cord
Reflex activities (walking, withdrawal from pain, leg support, control of blood flow
Control of respiration & arterial pressure
Emotion

3. Conduction generally occurs in one direction.
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

4. Signals Nerves deliver sequences of spikes.
Spike frequency translates to signal strength.
Time

5. Frequency of discharge (s-1)
Signals
Response threshold and maximum spike frequency depend on nerve type.
Note: Threshold for Neuron 3 has a higher threshold, but ultimately has higher frequency of discharge.
600
Neuron 1
500 3
Frequency of discharge (s-1)
400
300 2
200
100
Excitatory State

6. 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

7. 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

8. Drugs Increases Excitability (Reduced Threshold)
Caffeine, theophylline, theobromide (coffee, tea and cocoa, respectively)
Decrease Inhibition
Strichnine – can cause muscle spasms
Increase membrane threshold
Most anesthetics

9. Connections Synaptic cleft (2-3 nm wide) Presynaptic Terminal has
Mitochondria
Neural Transmitter Vesicles
Postsynaptic Terminal (cell soma) has:
Receptor Proteins
Transmitter Vesicles
Mitochondria
Soma
Receptor Proteins

10. Causes of Synaptic Delay
Discharge of neural transmitter.
Diffusion of the transmitter across the cleft.
Response of membrane receptor to the neural transmitter.
Action of the receptor to increase membrane permeability.
Inward diffusion of sodium.
Discharge
Na+
Receptor Response
Diffusion
Receptor Effect

11. Release of Neural Transmitter
Voltage gated Ca++ channels release Ca++
Ca++ causes release of neural transmitter.
Each vesicle secretes transmitter by pinocytosis.
Transmitter Acetylcholine
molecules per vesicle
Enough vesicles for 10,000 action potentials

12. 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)

13. Transmitter Substance
G Protein Receptors
Extracellular
Transmitter Substance  
Intracellular  
 Portion affects the neuron (e.g. opening potassium channel, transcription, enzyme activation)

14. 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

15. Action Potential Potential Inside (mV) -70 Time (ms) Influx of Na+
Potential Inside (mV)
-70
Time (ms)
Influx of Na+
Excessive K+ Inside
Outflux of Na+, Influx of K+

16. 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.

17. Mechanisms of Inhibition
Opening of chloride channels
makes inside more negative
Increasing K+ Conductance (K+ diffuses out)
Activation of inhibiting receptor enzymes

18. Neural Transmitters Approximately 50 neural transmitters are known.
Small molecules
Fast-acting
Acute responses
Large polypeptides
Slow-acting
Long-term responses

19. Neural Transmitters Factors in response
Amount of transmitter generated
Number of receptors
Transmitter uptake mechanisms
Transmitter inactivation
Receptor inactivation

20. 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

21. Recycling of Transmitter Vesicles

22. Recycling of Transmitter Vesicles
Concentrating Proteins

23. Recycling of Transmitter Vesicles
Concentrating Proteins

24. Recycling of Transmitter Vesicles

25. Small Neural Transmitters
Acetylcholine:
Excitation (mostly)
Norepinephrine:
Glutamate:
Excitation
Dopamine:
Inhibition
Glycine:
GABA:
Serotonin:
Pain inhibition, Sleep
Nitric Oxide (NO):
Memory, Smooth muscle relaxation, inhibits platelets and cellular proliferation. NO is not stored.

26. Selected Neuropeptides
Hypothalamic
Leuteinizing hormone
Pituitary
Growth Hormone
Vasopressin
Oxytocin
Acting on Gut and Brain
Insulin
Glucagon
Others
Angiotensin II
Bradykinin
Sleep Peptides

27. 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.

28. Response Time for Neural Transmitter
If L is 3 nm and D is 3.45 x 10-6 cm2/s (D for serotonin), then:
It follows that the transport of the neural transmitter across the synaptic cleft is not the time limiting factor in neural transmission.

29. Other Factors in Response Time
Release of transmitter.
Response time of receptors.
Response time for action after receptor response.

30. Connections Facilitated (subthreshold or subliminal) Zone
Discharge Zone
Transmitting nerve will trigger receiving nerve
Facilitated
Discharge

31. Connections Inhibition Zone
Exists when dendrites are inhibitory instead of excitatory.
Inhibition Zone
(entire field of inhibiting neuron)

32. 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

33. Divergence To increase the intensity on a given element:
To cause the same effect on different elements:

34. 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

35. Afterdischarge
Simplest case – neuronal signal feeds back on itself, causing re-triggering.

36. Afterdischarge with Facilitation/Inhibition
External Neuron
External neuron excites or inhibits the feedback connection.

37. Circuit Analogue to Oscillatory Pool
Schmitt Trigger (has hysteresis, positive feedback) + - R1
Saturation
Voltage (V)
Time (s)
Voltage (V)
Time (s)
Integrator
Substitute FET transistor for R1 to get voltage (signal) controlled oscillator.

38. 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

39. 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.

40. 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.

41. 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

42. Somatic Sensory Pathways
Dorsal Column
Touch signals for localization
Touch sensations for fine intensity
Phasic (e.g. vibratory) sensations
Position Sensations
Fine Pressure
Anterolateral System
Pain
Warm and Cold
Crude touch and pressure
Tickle and Itch
Sexual Sensations

43. 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
Slow burning pain
Aching pain
Throbbing pain
Nauseous pain
Chronic pain
Usually indicates tissue destruction

44. Purpose of Pain Patient: “Doctor, it hurts when I do this.”
Doctor: “Well, don’t do that!”

45. Pain Receptors All pain receptors are free nerve endings.
Pain receptors are found in:
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.

46. Types of Pain Stimuli Mechanical Thermal Chemical
Caused by bradykinin, serogonin, histamine, K+, acetylcholine, proteolytic enzymes
Enhanced by prostaglandins, substance P.

47. 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)

48. Pain Fibers Fast pain Slow, chronic pain
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
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

49. 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 (neurotrans-mitters) are involved.
Opiate system – Endorphins and Enkephalins
Inhibition by tactile sensory signals
E.g. rubbing the skin

50. 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).

51. 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)

52. Abnormal Pain Hyperalgesia (excitable pain pathway) Thalamic syndrome
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

53. Headache Brain is insensitive to pain
Regions around the brain are sensitive
Meninges
Nasal Sinuses
Venous sinuses
Tentorium
Dura

54. Types of Headache Migrane Meningitis
Cause is not well understood
May result from vessel spasm – vessel expands after the vessel is exhausted.
Meningitis
Infection of meninges
West Nile virus
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)

55. Thermal Sensations Warmth Receptors Heat Pain Cold Pain Cold Receptors
Impulses per Second 45 5 25 60
Temperature (ºC)

56. 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.