1. Fundamentals of the Nervous System and Nervous Tissue11
P A R T B
Fundamentals of the Nervous System and Nervous Tissue

2. Synaptic Transmission

3. Typically composed of two cells and the space between them:
Synapses
A junction that mediates information transfer from one neuron to another neuron or to an effector cell
Specialized for the release and reception of neurotransmitters (chemical communication)
Typically composed of two cells and the space between them:
Axonal terminal of the presynaptic neuron, which contains synaptic vesicles
Receptor region on the dendrite(s) or soma of the postsynaptic neuron

4. Fluid-filled space separating the presynaptic and postsynaptic neurons
Synaptic Cleft
Fluid-filled space separating the presynaptic and postsynaptic neurons
Prevents nerve impulses from directly passing from one neuron to the next
Transmission across the synaptic cleft:
Is a chemical event (as opposed to an electrical one)
Ensures unidirectional communication between neurons

5. Steps in Synaptic Transmission
Action potential reaches the axon terminal of the presynaptic neuron and opens Ca2+ channels (voltage gates)
Ca2+ enters axon terminal and causes vesicles to fuse with pre-synaptic membrane
Neurotransmitter is released from the vesicle into the synaptic cleft via exocytosis
Neurotransmitter diffuses across the synaptic cleft
Neurotransmitter binds to receptors on the postsynaptic neuron
Receptors open chemical gates, causing an excitatory or inhibitory effect which may cause the postsynaptic cell to fire an AP or block it
Neurotransmitter is inactivated, ending the chemical signal. Inactivation could be caused by enzymatic degradation or by reuptake of neurotransmitter into pre-synaptic cell.

6. Termination of Neurotransmitter Effects
Neurotransmitter bound to a postsynaptic neuron:
Produces a continuous postsynaptic effect
Blocks reception of additional “messages”
Must be removed from its receptor to end signals
Removal of neurotransmitters occurs when they:
Are degraded by enzymes
Are reabsorbed by astrocytes or the presynaptic terminals (known as reuptake)
Diffuse away from the synaptic cleft

7. Synaptic Delay
Neurotransmitter must be released, diffuse across the synapse, and bind to receptors
Synaptic delay – time needed to do this ( ms)
Synaptic delay is the rate-limiting step of neural transmission

8. Synaptic Transmission
Neurotransmitter
Ca2+
Na+
Axon terminal of
presynaptic neuron
Action potential
Receptor 1
Postsynaptic
membrane
Mitochondrion
Postsynaptic
membrane
Axon of
presynaptic
neuron
Ion channel open
Synaptic vesicles
containing
neurotransmitter
molecules 5
Degraded
neurotransmitter 2
Synaptic
cleft 3 4
Ion channel closed
Ion channel
(closed)
Ion channel (open)
Figure 11.18

9. Neurochemistry
The study of chemical interactions in the nervous system; primarily focused on neurotransmitter molecules, their receptor molecules, and the influences they have on the voltage potentials of neurons.

10. Neurotransmitter Molecules
Location
Functions
Other Info
Set up a chart like this to organize your notes from the next series of slides….

11. Neurochemistry: Neurotransmitters
Chemicals used for neuronal communication with the body and the brain
At least 50 different neurotransmitters have been identified
Classified chemically and functionally
Any single neuron only makes and releases ONE kind of neurotransmitter from ALL of its axon terminals
Any single neuron may have receptors for many kinds of neurotransmitters on its dendrites and soma

12. Types of Chemical Neurotransmitters
Acetylcholine (ACh)
Biogenic amines (Adrenaline, Dopamine, Serotonin, and others)
Certain Amino acids & Peptides (glycine, endorphins, GABA (Gamma  -AminoButyric Acid) and others
Novel messengers: ATP and dissolved gases such as NO and CO
 = Greek letter Gamma

13. First neurotransmitter identified, and best understood
Acetylcholine
First neurotransmitter identified, and best understood
Synthesized and enclosed in synaptic vesicles
Degraded by the enzyme acetylcholinesterase (AChE)
Released by:
All neurons that stimulate skeletal muscle (NMJ)
Some neurons in the autonomic nervous system
Some CNS neurons
Causes muscle contraction and autonomic activity

14. Broadly distributed in the brain
Biogenic Amines
Include:
Catecholamines – dopamine, norepinephrine (NE), and epinephrine
Indolamines – serotonin and histamine
Broadly distributed in the brain
Play roles in emotional behaviors, our biological clock, and more

15. Epinephrine & Norepinephrine
Epinephrine is the proper name for adrenaline
Used in the sympathetic nervous system (fight or flight) and in the CNS
Adrenal glands release epinephrine

16. Dopamine
Used in the CNS (basal ganglia)
Involved in integrating (combining) sensory inputs with motor outputs; also involved with the reward center and addictive behaviors
Low dopamine levels occur in patients with Parkinson’s disease – dopamine replacement therapy relieves their symptoms but does not cure the disease – stem cell transplants may allow a cure in the future

17. Synthesis of Catecholamines
Enzyme
The catecholamines are formed by converting one neurotransmitter into the next
The presence or absence of enzymes in the cell determine which neurotransmitter is formed
Figure 11.21

18. Serotonin
Used in CNS
Often plays an inhibitory role, helping to filter out excess stimuli

19. Dopamine & Serotonin Pathways

20. Peptides Include: GABA: inhibitory neurotransmitter
Substance P – mediator of pain signals
Endorphins and enkephalins: Act as natural opiates; reduce pain perception

21. Neurotransmitters: Novel Messengers
ATP
Is found in both the CNS and PNS
Provokes pain sensation
Nitric oxide (NO)
Is involved in learning and memory

22. Functional Classification of Neurotransmitters
Two classifications: excitatory and inhibitory
Excitatory neurotransmitters (e.g., glutamate) cause depolarizations by opening chemical gates for Na+
Inhibitory neurotransmitters (e.g., GABA and glycine) cause hyperpolarizations by opening chemical gates for Cl-

23. Functional Classification of Neurotransmitters
Some neurotransmitters have both excitatory and inhibitory effects
Different receptors for the same neurotransmitter result in either excitation or inhibition
Example: acetylcholine has 2 receptors called nicotinic and muscarinic
Excitatory at neuromuscular junctions with skeletal muscle (nicotinic receptor)
Inhibitory in cardiac muscle (muscarinic receptor – part of parasympathetic system)

24. Neurotransmitter Receptor Mechanisms
Direct: neurotransmitters that open ion channels
Promote rapid responses that quickly fade
Examples: ACh and amino acids
Indirect: neurotransmitters that act through second messengers such as cyclic AMP
Promote long-lasting but slower effects
Examples: biogenic amines, peptides, and dissolved gases
PLAY
InterActive Physiology ®:
Nervous System II: Synaptic Transmission

26. Neuropharmacology: Drug Interactions with Neurons
Drugs are chemicals that influence the physiology of the body
Psychoactive drugs are chemicals that influence the physiology of the brain
Psychoactive drugs may send false messages by enhancing the action of a neurotransmitter (these drugs are called agonists) or they may block true messages by preventing the action of a neurotransmitter (these drugs are known as antagonists)

27. Agonists may function in several ways:
Agonists (mimics)
Drugs that enhance the action of a specific neurotransmitter are called agonists
Regardless of HOW they function, they send false signals to the post-synaptic cell
Agonists may function in several ways:
Release extra neurotransmitter from vesicles
Block degradation or reuptake of neurotransmitter
Bind to the receptor and activate it, mimicking the neurotransmitter

28. Antagonists (blockers)
Drugs that block the action of a specific neurotransmitter are called antagonists
Regardless of HOW they function, they block true signals to the post-synaptic cell
Antagonists often function by binding to the receptor without activating it, blocking the neurotransmitter from sending its signal
Other possibilities include preventing NT release from vesicles, or blocking action potentials by keeping Na+ gates closed, etc.

29. Copy this chart in your notes and fill it out as you study each of the following slides. Notice that extra space is left for “Action” and “Comments.” Just copy the first row for now, since each row will be a different size.
Category
Drug
Neurotrans-mitter
Action
Comments
Etc.

30. Stimulants
Stimulants such as amphetamines and cocaine act primarily as catecholamine agonists
They increase release of norepinephrine and dopamine and also block their reuptake
Stimulants such as nicotine act as ACh agonists by binding to and activating receptors
Activates sympathetic nervous system quickly (direct action via chemical gates) and parasympathetic nervous system slowly (indirect action via second messengers)
Caffeine’s effects largely result from increasing blood flow to the brain

31. Depressants
Tranquilizers like valium act as agonists of GABA, an inhibitory neurotransmitter
They increase the binding of GABA to its receptor
This results in greater inhibition of APs in the CNS
Alcohol acts on multiple types of neurons, but does not act on the synapse
It reduces the flow of Na+ across membranes, interfering with action potentials
Neurons respond more slowly or not at all

32. Narcotics
Opium, morphine, and heroin are agonists of endorphins
Bind to and activate endorphin receptors
Block pain, induce euphoria
Endorphins were discovered by scientists trying to determine how opiates influenced the brain
Endorphin levels increase in women about to give birth, and they increase slightly during exercise (resulting in the “runner’s high”)

33. Hallucinogens
Widespread effects by drugs such as LSD, mescaline, and psilocybin
One aspect of their action is acting as antagonists to serotonin
Bind to and block serotonin receptors
Serotonin’s role in filtering excess stimuli is thereby reduced – the extra stimulation could be perceived as a hallucination

34. Hallucinogens
Marijuana is sometimes classified as a hallucinogen – its active ingredient is THC (tetra hydra cannibanol)
Its mechanism of action is unclear – it seems to influence multiple types of neurons
More research is needed
Like tobacco, inhaling any form of smoke is harmful to the lungs – marijuana may be worse since it is usually smoked without a filter and each inhalation may leave more deposits than a cigarette. However, the amount of marijuana smoked is usually less than for tobacco.

35. Neurotoxins 1 – Poisonous Drugs
These drugs may be used for experimental purposes, because they can isolate the action of different neurotransmitter systems. Some of them also have uses beyond research.
Curare & Tetrodotoxin – ACh antagonist at NMJ, binding irreversibly to receptors, causes paralysis and suffocation – once collected from frogs and used on poison arrows by South American natives – useful for frogs by protecting them from predators (tetrodo.is from pufferfish)
Botox (botullism toxin, produced by bacteria) – Blocks release of ACh from vesicles at NMJ, causes paralysis

36. Neurotoxins 2 – Poisonous Drugs
Nicotine – large doses result in complete tetanus due to activating ACh receptors at the NMJ – commonly used as an insecticide and probably evolved for this purpose in the tobacco plant
Convulsants – block the enzyme that synthesizes GABA. Since GABA is an inhibitory neurotransmitter, the lack of inhibition allows neurons to have more APs than normal, resulting in convulsions.

37. Antipsychotics and Antidepressants
These drugs are used to treat psychological conditions, but are not used recreationally
Antipsychotics reduce symptoms of schizophrenia; they act by blocking dopamine receptors
Antidepressants reduce symptoms of clinical depression; there are different types, but one acts by blocking the action of the enzyme that breaks down dopamine, epinephrine, and norepinephrine (“MAO inhibitors” – monoamine oxidase)

38. Fundamentals of the Nervous System and Nervous Tissue11
P A R T C
Fundamentals of the Nervous System and Nervous Tissue

39. Nerve Fiber Classification
Nerve fibers are classified according to:
Diameter
Degree of myelination
Speed of conduction

40. Synapses
Figure 11.17

41. Other types of synapses include:
Axodendritic – synapses between the axon of one neuron and the dendrite of another
Axosomatic – synapses between the axon of one neuron and the soma of another
Other types of synapses include:
Axoaxonic (axon to axon)
Dendrodendritic (dendrite to dendrite)
Dendrosomatic (dendrites to soma)
PLAY
InterActive Physiology ®:
Nervous System II: Anatomy Review, page 5

42. Electrical Synapses Electrical synapses:
Are less common than chemical synapses
Correspond to gap junctions found in other cell types
Are important in the CNS in:
Arousal from sleep
Mental attention
Emotions and memory
Ion and water homeostasis
PLAY
InterActive Physiology ®:
Nervous System II: Anatomy Review, page 6

43. Synaptic Cleft: Information Transfer
Ca2+
Axon terminal of
presynaptic neuron
Action potential 1
Axon of
presynaptic
neuron
Figure 11.18

44. Synaptic Cleft: Information Transfer
Ca2+
Axon terminal of
presynaptic neuron
Action potential 1
Mitochondrion
Axon of
presynaptic
neuron
Synaptic vesicles
containing
neurotransmitter
molecules 2
Figure 11.18

45. Synaptic Cleft: Information Transfer
Ca2+
Axon terminal of
presynaptic neuron
Action potential 1
Postsynaptic
membrane
Mitochondrion
Axon of
presynaptic
neuron
Synaptic vesicles
containing
neurotransmitter
molecules 2
Synaptic
cleft 3
Ion channel
(closed)
Ion channel (open)
Figure 11.18

46. Synaptic Cleft: Information Transfer
Neurotransmitter
Ca2+
Na+
Axon terminal of
presynaptic neuron
Action potential
Receptor 1
Postsynaptic
membrane
Mitochondrion
Postsynaptic
membrane
Axon of
presynaptic
neuron
Ion channel open
Synaptic vesicles
containing
neurotransmitter
molecules 2
Synaptic
cleft 3 4
Ion channel
(closed)
Ion channel (open)
Figure 11.18

47. Synaptic Cleft: Information Transfer
Neurotransmitter
Ca2+
Na+
Axon terminal of
presynaptic neuron
Action potential
Receptor 1
Postsynaptic
membrane
Mitochondrion
Postsynaptic
membrane
Axon of
presynaptic
neuron
Ion channel open
Synaptic vesicles
containing
neurotransmitter
molecules 5
Degraded
neurotransmitter 2
Synaptic
cleft 3 4
Ion channel closed
Ion channel
(closed)
Ion channel (open)
Figure 11.18

48. Postsynaptic Potentials
Neurotransmitter receptors mediate changes in membrane potential according to:
The amount of neurotransmitter released
The amount of time the neurotransmitter is bound to receptors
The two types of postsynaptic potentials are:
EPSP – excitatory postsynaptic potentials
IPSP – inhibitory postsynaptic potentials
PLAY
InterActive Physiology ®:
Nervous System II: Synaptic Transmission, pages 7–12

49. Excitatory Postsynaptic Potentials
EPSPs are graded potentials that can initiate an action potential in an axon
Use only chemically gated channels
Na+ and K+ flow in opposite directions at the same time
Postsynaptic membranes do not generate action potentials

50. Excitatory Postsynaptic Potential (EPSP)
Figure 11.19a

51. Inhibitory Synapses and IPSPs
Neurotransmitter binding to a receptor at inhibitory synapses:
Causes the membrane to become more permeable to potassium and chloride ions
Leaves the charge on the inner surface negative
Reduces the postsynaptic neuron’s ability to produce an action potential

52. Inhibitory Postsynaptic (IPSP)
Figure 11.19b

53. Summation
A single EPSP cannot induce an action potential
EPSPs must summate temporally or spatially to induce an action potential
Temporal summation – presynaptic neurons transmit impulses in rapid-fire order

54. IPSPs can also summate with EPSPs, canceling each other out
Summation
Spatial summation – postsynaptic neuron is stimulated by a large number of terminals at the same time
IPSPs can also summate with EPSPs, canceling each other out
PLAY
InterActive Physiology ®:
Nervous System II: Synaptic Potentials

55. Summation
Figure 11.20

56. Neurotransmitters: Acetylcholine
Degraded by the enzyme acetylcholinesterase (AChE)
Released by:
All neurons that stimulate skeletal muscle
Some neurons in the autonomic nervous system

57. Channel-Linked Receptors
Composed of integral membrane protein
Mediate direct neurotransmitter action
Action is immediate, brief, simple, and highly localized
Ligand binds the receptor, and ions enter the cells
Excitatory receptors depolarize membranes
Inhibitory receptors hyperpolarize membranes

58. Channel-Linked Receptors
Figure 11.22a

59. G Protein-Linked Receptors
Responses are indirect, slow, complex, prolonged, and often diffuse
These receptors are transmembrane protein complexes
Examples: muscarinic ACh receptors, neuropeptides, and those that bind biogenic amines

60. G Protein-Linked Receptors: Mechanism
Neurotransmitter binds to G protein-linked receptor
G protein is activated and GTP is hydrolyzed to GDP
The activated G protein complex activates adenylate cyclase

61. G Protein-Linked Receptors: Mechanism
Adenylate cyclase catalyzes the formation of cAMP from ATP
cAMP, a second messenger, brings about various cellular responses

62. Neurotransmitter Receptor Mechanism
Ions flow
Blocked ion flow
Ion channel
Adenylate
cyclase
Channel closed
Channel open
(a)
Neurotransmitter (ligand)
released from axon terminal
of presynaptic neuron
PPi
GTP 4 5
Changes in
membrane
permeability
and potential 3 1
cAMP
ATP 5 3
GTP
Enzyme
activation
Protein
synthesis 2
GDP
GTP
Receptor
Activation of
specific genes
G protein
(b)
Nucleus
Figure 11.22b

63. Neurotransmitter Receptor Mechanism
Ions flow
Blocked ion flow
Channel closed
Channel open
(a)
Neurotransmitter (ligand)
released from axon terminal
of presynaptic neuron 1
Receptor
G protein
(b)
Figure 11.22b

64. Neurotransmitter Receptor Mechanism
Ions flow
Blocked ion flow
Adenylate
cyclase
Channel closed
Channel open
(a)
Neurotransmitter (ligand)
released from axon terminal
of presynaptic neuron 1
GTP 2
GDP
GTP
Receptor
G protein
(b)
Figure 11.22b

65. Neurotransmitter Receptor Mechanism
Ions flow
Blocked ion flow
Adenylate
cyclase
Channel closed
Channel open
(a)
Neurotransmitter (ligand)
released from axon terminal
of presynaptic neuron
GTP 3 1 3
GTP 2
GDP
GTP
Receptor
G protein
(b)
Figure 11.22b

66. Neurotransmitter Receptor Mechanism
Ions flow
Blocked ion flow
Adenylate
cyclase
Channel closed
Channel open
(a)
Neurotransmitter (ligand)
released from axon terminal
of presynaptic neuron
PPi
GTP 4 3 1
cAMP
ATP 3
GTP 2
GDP
GTP
Receptor
G protein
(b)
Figure 11.22b

67. Neurotransmitter Receptor Mechanism
Ions flow
Blocked ion flow
Adenylate
cyclase
Channel closed
Channel open
(a)
Neurotransmitter (ligand)
released from axon terminal
of presynaptic neuron
PPi
GTP 4 5
Changes in
membrane
permeability
and potential 3 1
cAMP
ATP 5 3
GTP
Enzyme
activation
Protein
synthesis 2
GDP
GTP
Receptor
Activation of
specific genes
G protein
(b)
Nucleus
Figure 11.22b

68. Neurotransmitter Receptor Mechanism
Ions flow
Blocked ion flow
Ion channel
Adenylate
cyclase
Channel closed
Channel open
(a)
Neurotransmitter (ligand)
released from axon terminal
of presynaptic neuron
PPi
GTP 4 5
Changes in
membrane
permeability
and potential 3 1
cAMP
ATP 5 3
GTP
Enzyme
activation
Protein
synthesis 2
GDP
GTP
Receptor
Activation of
specific genes
G protein
(b)
Nucleus
Figure 11.22b

69. G Protein-Linked Receptors: Effects
G protein-linked receptors activate intracellular second messengers including Ca2+, cGMP, diacylglycerol, as well as cAMP
Second messengers:
Open or close ion channels
Activate kinase enzymes
Phosphorylate channel proteins
Activate genes and induce protein synthesis

70. Neural Integration: Neuronal Pools
Functional groups of neurons that:
Integrate incoming information
Forward the processed information to its appropriate destination

71. Neural Integration: Neuronal Pools
Simple neuronal pool
Input fiber – presynaptic fiber
Discharge zone – neurons most closely associated with the incoming fiber
Facilitated zone – neurons farther away from incoming fiber

72. Simple Neuronal Pool
Figure 11.23

73. Types of Circuits in Neuronal Pools
Divergent – one incoming fiber stimulates ever increasing number of fibers, often amplifying circuits
Figure 11.24a, b

74. Types of Circuits in Neuronal Pools
Convergent – opposite of divergent circuits, resulting in either strong stimulation or inhibition
Figure 11.24c, d

75. Types of Circuits in Neuronal Pools
Reverberating – chain of neurons containing collateral synapses with previous neurons in the chain
Figure 11.24e

76. Types of Circuits in Neuronal Pools
Parallel after-discharge – incoming neurons stimulate several neurons in parallel arrays
Figure 11.24f

77. Patterns of Neural Processing
Serial Processing
Input travels along one pathway to a specific destination
Works in an all-or-none manner
Example: spinal reflexes

78. Patterns of Neural Processing
Parallel Processing
Input travels along several pathways
Pathways are integrated in different CNS systems
One stimulus promotes numerous responses
Example: a smell may remind one of the odor and associated experiences

79. Development of Neurons
The nervous system originates from the neural tube and neural crest
The neural tube becomes the CNS
There is a three-phase process of differentiation:
Proliferation of cells needed for development
Migration – cells become amitotic and move externally
Differentiation into neuroblasts

80. Axonal Growth Guided by: Scaffold laid down by older neurons
Orienting glial fibers
Release of nerve growth factor by astrocytes
Neurotropins released by other neurons
Repulsion guiding molecules
Attractants released by target cells

81. N-CAMs
N-CAM – nerve cell adhesion molecule
Important in establishing neural pathways
Without N-CAM, neural function is impaired
Found in the membrane of the growth cone