1. Pharmacology of Central Nervous System

3. The Functions of Neuron and Neuroglia
Section 1
The Functions of Neuron and Neuroglia

4. General consideration
1.composition of nervous system
(1)central and peripheral nervous systems
(2)neuron and synapse*

6. The elementary functions of neuron
Receive the excitations or inhibitions induced by internal or external stimulations.
(2)Analyze and integrate the information from every organs.

7. The elementary functions of neuron
(3)Generate or carry the demands regulating the activities of the effectors.
(4)Some neurons have neuroendocrine function.

8. Neurons have 4 important zones
Soma and dendrites –receive the information,generate and integrate the local potential changes.
Initial segment - action potentials are generated.

9. Neurons have 4 important zones
Axon process –
Nerve endings
transmits the impulses to the nerve endings.
- release the synaptic transmitters.

11. Neurotrophin Nerve growth factor(NGF)
Brain-derived neurotrophin factor(BDNF)
Neurotrophin 3
Neurotrophin 4/5
Neurotrophin 6
Ciliary neurotrophin factor(CNTF)
Glial cell-derived neurotrophin factor(GDNF)
Insulin-like growth factorⅠ(IGF-Ⅰ)
Transforming growth factor(TGF)

12. Neuroglia About 1.0×1012~ 5.0×1012 neuroglia cells ,
10~50 fold of neurons
Dendrites and axons can not be distinguished clearly
No synapse formed and no AP produced

15. The types of glial
CNS astrocyte
oligodendrocyte
microglia

16. Functions of glial cells
Astrocytes (Astroglia)
- Support the neurons
- Clean up brain "debris"( damaged material)
and fill in the damaged area
- Transport nutrients to neurons

17. Functions of glial cells
Astrocytes (Astroglia)
- regulate the external chemical environment of
neurons by removing excess ions
and recycling neurotransmitters.

18. Oligodendrocytes (1) insulate the axons
- myelinated axons
(1) insulate the axons
(2) facilitate the conduction of electrical impulses.

19. Microglia - remove most of the waste and cellular debris from the CNS
- act as the immune cells of the CNS
- remove most of the waste and cellular debris from the CNS
- derivation,action in brain injury, action in other diseases.

20. General interactions between neurons
Section 2
General interactions
between neurons

21. Typical Synapses (chemical synapses)
The small gap or space between the axon terminals of one neuron and the dendrites or cell body of the next neuron is called the Synapse .

22. Structure of Synapse Membrane of presynaptic neuron Synaptic cleft
Membrane of postsynaptic neuron

23. Major types of SynapsesC
A: axo-somatic synapse
B：axo-dendritic synapse
C：axo-axonic synapse B A

24. Classifications of Synapses
– Chemical synapses
▪Directed synapses (Typical synapses)
▪Non- directed synapses (Varicosity)
– Electrical synapses

25. Typical Synapses (chemical synapses)

26. Process of Typical Synaptic Transmission

27. Process of Typical Synaptic Transmission
1. An arriving action potential depolarizes the presynaptic membrane.
2. Calcium ions enter the cytoplasma of the synaptic knob
3. Neurotransmitters release.

28. Process of Typical Synaptic Transmission
4. Neurotransmitters diffuse to and bind to the receptors on postsynaptic membrane.

29. Process of Typical Synaptic Transmission
5. Receptors on the postsynaptic membrane are activated, producing a postsynaptic potential.
6. Neurotransmitters are broken down.

30. Electrical Activities of Postsynaptic Neurons (Postsynaptic Potential)
Forms of the postsynaptic potential
Excitatory postsynaptic potential (EPSP)
Inhibitory postsynaptic potential (IPSP)

31. Postsynaptic Potentials
Excitatory postsynaptic potential
Inhibitory postsynaptic potential

32. Postsynaptic Potentials
When a neuron responds to the neurotransmitter postsynaptically,
it allows ions to move across its membrane.

33. Postsynaptic Potentials
The movement of ions changes the membrane potential of the postsynaptic neuron.
It is called the “postsynaptic potential”.

34. EPSP

35. EPSP Excitatory transmitters → Synaptic cleft →
bind to receptors → ↑the postsynaptic membrane's permeability to Na+, Ca2+ → enter the postsynaptic neuron →produce a
depolarizing potential.

36. IPSP

37. IPSP
Inhibitatory transmitters → Synaptic cleft → bind to receptors →  the postsynaptic membrane’s permeability to Cl-（or K+ ） → Cl- enter the postsynaptic neuron →generate a hyperpolarizing potential.

38. The EPSP is produced by depolarization of the postsynaptic membrane.
During this potential, the excitability of the neuron to other stimuli is increased,
This the potential is called the EPSP.

39. The IPSP is produced by hyperpolarization of the postsynaptic membrane.
During this potential, the excitability of the neuron to other stimuli is decreased,
This the potential is called the IPSP.

40. Neurotransmitters 40

41. Neurotransmitters Noradrenaline (NA) Dopamine (DA)
5-HT (5-hydroxytryptamine)
Acetylcholine (ACh)
Glutamate
GABA (γ-aminobutyric acid)
monoamines
amino acids 41

42. Common features of neurotransmitters
Synthesis
Storage & release
Interaction with target cell
Termination of action 42

43. Synthesis -enzymes synthetic enzymes precursor uptake
Neurotransmitters are synthesised from precursors by the action of enzymes
e.g. DA synthesised from tyrosine by tyrosine hydroxylase and DOPA decarboxylase 43

44. Storage of transmitters- vesicles
storage vesicles
Neurotransmitters are stored in vesicles
Protected from metabolic enzymes
Ready for release 44

45. Release of transmitter-exocytosis
Depolarization of the terminal causes Ca++ dependent exocytosis
Voltage sensitive Ca++ channels open
Vesicles fuse with presynaptic membrane and empty into synaptic cleft
Action potential
exocytosis 45

46. Interaction with target cell -receptors**
Presynaptic
neurone
Post-synaptic
neurone 46

47. Termination of action-reuptake
Monoamines & amino acids
High affinity reuptake removes transmitter from the synaptic cleft
Metabolic
enzymes 47

48. Termination of action- metabolism
Extraneuronal metabolism inactivates transmitter
choline is recycled
Acetylcholine
Metabolic
enzyme 48

49. Interaction with target cell-receptors
Presynaptic
neurone
Post-synaptic
neurone
Receptors
Excitatory/inhibitory
Ligand-gated ion channel
G-protein linked 49

52. Ligand-gated ion channels
Allosteric change
opens channel
ion channel
ION
Ions can enter
(or leave) cell 52

53. Ligand-gated ion channels
Receptor with binding site linked directly to an ion channel
Binding to the receptor opens the channel
Channels are ion selective
Ions enter or leave the cell altering membrane potential 53

54. Ligand-gated ion channels
NMDA (glutamate)
Ach
5-HT3
GABAA
Na+ (Ca++) channels
excitatory
Cl- channel
inhibitory 54

55. G-protein linked receptors
Ions G G G
Enzyme
+/-
+/-
Second messengers (cAMP, PI)
Changes in
excitability
Calcium
release
Other
Protein
phosphorylation
Cellular effects 55

56. G-protein linked receptors
Receptor in which binding site is linked to a G protein
Binding to the receptor
activates enzymes  ‘second messengers’
opens ion channels
Effects are slow and often modulatory 56

57. Neurotransmitters

58. Acetylcholine
first compound to be identified pharmacologically as a transmitter in the CNS.

59. Most CNS responses to acetylcholine are mediated by a large family of G protein-coupled muscarinic receptors

60. A number of pathways contain acetylcholine
neostriatum
A number of pathways contain acetylcholine
medial septal nucleus
the reticular formation

61. Cholinergic pathways
play an important role in cognitive functions, especially memory.

62. Excitatory：glutamate，
Amino acid and receptor
Excitatory：glutamate，
Inhibitory：GABA ，glycine
     

63. ② metabotropic receptor
Amino acid and receptor
 a. Glu
  in cerebral cortex and sensory afferents
     receptor：① ionotropic receptor：
            KA，AMPA，NMDA
② metabotropic receptor

64. Glutamate
Excitatory synaptic transmission is mediated by glutamate, which is present in very high concentrations in excitatory synaptic vesicles .
Glutamate is released into the synaptic cleft by Ca2+-dependent exocytosis.

65. Glutamate
The released glutamate acts on postsynaptic glutamate receptors
Cleared by glutamate transporters present on surrounding glia.

66. Glutamate
In glia, glutamate is converted to glutamine by glutamine synthetase
Released from the glia,
taken up by the nerve terminal,
converted back to glutamate by the enzyme glutaminase.

67. Glutamate
The high concentration of glutamate in synaptic vesicles is achieved by the vesicular glutamate transporter (VGLUT).

68. The ionotropic receptors divided into three subtypes :
amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)
kainic acid (KA) 
N -methyl-D -aspartate (NMDA).

69. A typical excitatory synapse contains AMPA receptors, which tend to be located toward the periphery,
NMDA receptors, which are concentrated in the center.

70. Kainate receptors
Kainate receptors being expressed at high levels in the hippocampus, cerebellum, and spinal cord

71. in cerebral cortex and cerebrum corpus striatum
b. GABA
in cerebral cortex and cerebrum corpus striatum
Receptor GABAA（ionotropic receptor） permeability for Cl-↑
GABAB（G-protein coupled receptor）:
permeability for K+↑and for Ca2+↓

72. The cerebellum - lateral vestibular nucleus;
GABA pathways:
The cerebellum - lateral vestibular nucleus;
Striatum – substantia nigra

74. Dopamine

75. Four pathway of dopaminergic neurotransmission
1.limbic system- mesencephalic pathway emotion 2.cortico- mesencephalic pathway thinking and motion

76. Four pathway of dopaminergic neurotransmission
3.nigrostriatum pathway motion 4.hypothalamo-hypophysis pathway endocrine

77. DA receptor and neural illness
(1) DA of the substantia nigra striatum pathways can result in Parkinson's disease;
(2) D2 receptor of limbic system- mesencephalic pathway and cortico- mesencephalic pathway can lead to schizophrenia.

79. 5 - HT : to participate in the activities of cardiovascular
awakening - a sleep cycle
pain
mental emotional activities
the regulation of the hypothalamus - pituitary neuroendocrine activity.

82. e.g. antiepileptics anaesthetics (1)axon: 4.Mechanism of drugs on CNS
slow/block axonal electrical conduction
e.g. antiepileptics
anaesthetics

83. 4.mechanism of drugs on CNS
(2)synapse: most drugs
①affect transmitter:
synthesis, storage, release, reuptake.
e.g. antidepressants

84. 4.mechanism of drugs on CNS
(2)synapse: most drugs
②affect receptor: activation/inhibition(block)
e.g. benzodiazepines, antipsychotics
③directly act on ion channels
e.g. phenytoin

85. 5.BBB Structure barrier between blood and brain cell;
3 parts barrier between blood and cerebrospinal
fluid
barrier between brain cell and cerebrospinal
fluid.

86. (2)function: restrict passage of polar compounds and macromolecules from blood into brain
(3)Pharmacological significance: prerequisite
e.g. penicillin----meningitis

87. SUMMARY

88. Activity of neuron(conduction of nervous impulse)
(1) neurotransmitter:
①NA, ACh, DA, GABA, glutamate, glycine, 5HT, histamine, opioid peptides, (excitatory/ inhibitory).
②biosynthesis, storage, release, degradation, reuptake.*

89. (2)receptor *

90. (3)conduction of impulse cross synapse: presynaptic neuron release neurotransmitter synaptic cleft neurotransmitter interacts with receptor neurotransmitter-receptor complex initiates a sequence of events (open ion channel) modulate the electrical activity of the postsynaptic neuron (depolarization/ hyperpolarization). *