Lecture 6 - Synapses Flashcards

1
Q

How many synapses are there in the human cortex?

A

Neurons - 20 billion
Over 1000 synapses per neuron
Total: 20 trillions I.e > 20 x 10^12

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2
Q

What are some synapses?

A

Excitatory

Increasing the response of a post-synaptic neuron

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3
Q

What are some examples of excitatory neurotransmitters?

A

Glutamate

ACH

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4
Q

What are some examples of inhibitory neurotransmitters?

A

GABA

Glycine

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5
Q

What determines the neurotransmitter action?

A

The properties of the receptors

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6
Q

Why did B.Katz win the Nobel prize?

A

Understanding quintal neurotransmission

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7
Q

What did B.Katz work on?

A

Nerve muscle junction

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8
Q

How are neurotransmitters released into a synapse?

A

Packaged vesicles called quanta

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9
Q

What does one quantum generate?

A

Miniature end plate potential

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10
Q

What is miniature end plate potential?

A

Smallest amount of stimulation that one neuron can send to another neuron

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11
Q

What is Quantal release a mechanism of?

A

Most traditional endogenous neurotransmitters are transmitted throughout the body

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12
Q

What 2 types of molecules does chemical neurotransmission rest on?

A

Chemical messengers

Chemically gated receptors

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13
Q

What plays an important role in giving rise to a negative membrane potential?

A

Electrochemical gradient for K+ ions

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14
Q

Why is ACH receptor not selective between sodium and potassium ions?

A

It has a reversal potential of 0 millivolts

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15
Q

Ena

A

Positive

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16
Q

Ek

A

Negative

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17
Q

NACh receptors

A

Ionotropic receptors

Respond to chemical stimulus and incorporate an ion channel

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18
Q

What is the structure of NACh receptors?

A

Formed from 5 subunits

Subunits have alpha helical domain

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19
Q

What happens in the absence of ACH?

A

H20 is being excluded

Alpha helices are stuck together

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20
Q

What holds the channels closed?

A

Hydrophobic interactions

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21
Q

Where does ACH bind?

A

At C loops on the alpha subunit

Outside the inter membrane domain

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22
Q

What helps shape the ACH binding pockets?

A

Gamma or delta subunit

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23
Q

Where was 2 sharp micro electrode inserted into muscle fibre?

A

One close to NMJ

The other can move at flick of switch

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24
Q

How is synaptic potential generated?

A

When you send action potential down the motor axon that is connected to muscle fibre

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25
Q

What happens to the micro electrode close to the NMJ?

A

Rapid rising of EPP

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26
Q

What is NMJ?

A

High-fidelity junction

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27
Q

What happens when you move the microelectrode further away?

A

The EPP gets smaller
Rise of EPP gets smaller
(Moving away from the source of depolarising current)

28
Q

What does muscle fibre membrane have?

A

Capacitance

29
Q

What is the source of excitation in muscle fibre?

A

End plate

30
Q

What was NMJ initiating?

A

Excitation in the muscle fibre

31
Q

What does a single quantum cause?

A

Only a slight depolarisation

32
Q

What happens when the electrode is inserted into muscle fibre very close to the NMJ?

A

Send impulses down motor axon

Record AP

33
Q

What occurs when electrode is recorded away from end plate?

A

No EPP is seen

Just AP

34
Q

How are tiny little blips recorded?

A

If amplifier is increased when electrode is near NMJ

35
Q

What occurs spontaneously in muscle fibre?

A

Tiny miniature potential

36
Q

How is the release of neurotransmitters at NMJ controlled?

A

Electrically

37
Q

What kind of recording is done in a muscle fibre?

A

Intracellular

38
Q

What is the release of neurotransmitter from presynaptic terminal dependent upon?

A

Presence of Ca2+

39
Q

Where must Ca2+ enter to trigger the release of neurotransmitter?

A

Pre-synaptic terminal

40
Q

What is not random but related?

A

The relationship between releasing neurotransmitters and the size of EPP recorded in a muscle fibre

41
Q

How is EPP generated?

A

Release of many N.T

42
Q

What is present on the post-synaptic membrane?

A

Junctional folds

43
Q

What is Acetylcholinesterase?

A

the enzyme that is responsible for breaking down ACH and terminating it’s action

44
Q

What is the role of Snare proteins?

A

Mediate vesicle fusion

45
Q

What is snare protein a primary target of?

A

Botulinum

Tetanus toxins

46
Q

What does synaputogamin-1 induce?

A

Transduction the Ca2+ signal into membrane “bending”

47
Q

What is present in the synaptic cleft?

A

Acetylcholinesterase

48
Q

What can neurotransmitter breakdown be inhibited by?

A

Organophosphate nerve agent
e.g. sarin (nerve gas)
Insecticide

49
Q

What is neurotransmitter breakdown medicinally inhibited by?

A

Neostigmine

Physostigmine

50
Q

What are the reasons for chemical transmission at NMJ?

A

Presence of miniature and analysis of EPP amplitude suggest transmission is based on quantal mechanism
Functional synaptic transmission requires entry of Ca2+ into presynaptic terminal
Presynaptic terminal typically contain membrane bound vesicles
EM: exocytosis of vesicles takes place with nerve stimulation, and that neurotransmitter is released into synaptic cleft
Transmission is unidirectional
Protein complex involved in exocytosis require Ca2+ entry
Nicotine acetylcholine receptors are found expressed at postsynaptic membrane
Immunohistochemical data puds Acetylcholinesterase in post junctional gold
Blocking NT release or breakdown alters characteristic of transmission
Autoantibodies against acetylcholine receptors cause myasthenia graves

51
Q

What does neurotransmitter release in CNS cause?

A

EPSP
IPSP
In the postsynaptic cell

52
Q

EPSP

A

1a afferent reflex arc
Reflex that give rise to knee jerk
Hamstring contain muscle spindle
When you hit the ligament it is stretched
Give rise to AP/impulse which go up the sensory pathway
Make monosynaptic connection with a same motor neuron
Alpha motor neuron sits in the central horn of spinal cord and connects to same muscle

53
Q

What is Glutamate receptor?

A

Excitatory synapse that give rise to depolarisation

Glutamate receptor: ionotropic

54
Q

What does a central axon lead to?

A

Pre-synapse

55
Q

What are examples of glutamate receptors?

A

Kinate receptors
NMDAR
AMPA

56
Q

What is Dales principle?

A

Each synaptic connection made by a single neuron utilises the same chemical transmitter

57
Q

Renshaw Inhibition

A

The first functional central circuit to be discovered
Inhibitory neuron: grey matter of spinal cord
Associate 2 ways:
Receive excitatory collateral from alpha neurons axon as they emerge from motor root and informed of how vigorously that neuron is firing
Renshaw cell synapses with multiple neuron
Elicit IPSP in alpha motor
1a inhibitory internueon and gamma motor neuron

58
Q

What is reciprocal antagonist inhibition?

A

When the CNS sends a message to agonist muscle to contract, the tension in Antagonist muscle is inhibited by impulses from motor neuron and thus must simultaneously relax

59
Q

Mechanism of IPSP

A
Glycine/GABA a receptor 
Ionotropic receptor 
Linked with an ion channel 
Cl- crosses the membrane 
Give rise to hyperpolarisation
60
Q

What is Risus sardonicus?

A

High characteristic, abnormal sustained spasm of facial muscle that appears to produce grinning

61
Q

Where is Glutamate taken up in?

A

Pre and post synaptic terminals and into adjacent glia

The transporter uses energy stored in the transmembrane Na* gradient to uptake glutamate

62
Q

Synaptic plasticity

A

Long lasting potentiation
Record extracellularly in dentate gyrus
Extracellular recording is altered by tetanizing activating performant path at high frequency
Synaptic depression and potentiation are both apparent in CA1 region of hippocampus

63
Q

What is LTD linked with

?

A

Activation of G protein coupled glutamate receptors morning

64
Q

Dudek + Bear

A

CA1 hippocampus (pyramidal neurons)
If you use 3hg to excite an input pathway to CA1
You can depress the synapse (LtD)
If you use 10hg stimulation - no long term effect on synaptic strength
50hg briefly —> generate LTP

65
Q

Long term synaptic plasticity

A

Memory storage

66
Q

What is the molecular mechanism of sensitisation in Aplysia?

A

Activate 5HT receptors
Release serotonin which acts on G protein coupled receptors
Activated pka
Action on potassium channels
Increase pka = translocated into the nucleus
Gives rise to the activation of protein synthesis
When KREB1 and KREB2 are bound together in the nucleus of a sensory neuron - become inactive