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Module 2 - Synaptic Molecular Anatomy Flashcards

1
Q

What are the properties of Electrical Synapses?

A

Electrical current flows through gap junctions bidirectionally, is very fast

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2
Q

Most transmission in the CNS occurs at what?

A

Chemical synapses

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3
Q

What are the neurotransmitters involved with chemical synapses?

A

Glutamate (Stimulatory) and GABA (Inhibitory)

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4
Q

What are the two types of Synaptic vesicles?

A

Small vesicles and Large dense core vesicles (LDCV)

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5
Q

What are the properties of Small vesicles?

A

50 nm diameter, Electron-lucent (clear), membrane bound and contain classic neurotransmitters e.g. Glutamate and GABA

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6
Q

What are the properties of Large Dense Core Vesicles?

A

100nm in Diameter, Electron-dense (Dark), membrane bound and contains catecholamines (adrenaline + noradrenaline), Neurotr0phins (BDNF), Neuropeptides (Neuropeptide Y) and Peptide Hormones (Growth Hormone)

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7
Q

What are the main locations of LDCV’s?

A

The Peripheral nervous system (Sympathetic Neurons), Hypothalamus, Neuroendocrine cells and Neurosecretory cells

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8
Q

What are the other properties of LDCV’s?

A

Comprise 1-2% of vesicles, release peptides and neuromodulators, are slow release, can occur outside active zones, act on G protein coupled receptors and Tyrosine Kinase receptors and effects can be pre and postsynaptic

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9
Q

What are the classifications of the Small synaptic vesicle pools?

A

The readily releasable pool (SSV’s docked at active zone), Reserve pool (Distal to active zone, associated with cytoskeleton) and the recycling pool (Diffusing).

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10
Q

What is the Synaptic vesicle life cycle?

A

Formed in Golgi apparatus and transported along microtubules to axons, Filled in axon terminals, stored in axon terminals, release neurotransmitter, recycled via endocytosis by endosomes or reserve pool and refilled by transporters

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11
Q

What are the three snare proteins associated with neurotransmitter release?

A

V-snare (Synaptobrevin), t-snare (SNAP25) and t-snare (Syntaxin)

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12
Q

What is the function of SNARE molecules?

A

involved in the docking of vesicles and the release of neurotransmitters

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13
Q

Translocation and docking during Neurotransmitter release requires what?

A

RAB proteins

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14
Q

What is the function of Synaptotagmin?

A

In binds calcium which is used in vesicle fusion and release

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15
Q

What are the two forms of neurotransmitter exocytosis?

A

Full-collapse fusion and “kiss and run”

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16
Q

What is the process of full collapse fusion exocytosis

A

Vesicles collapse into the plasma membrane and release all contents

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17
Q

What is the process of “kiss and run” exocytosis?

A

The fusion pore opens and closes and not all of the content is released.

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18
Q

What does Clathrin do?

A

Clathrin forms a coated pit on the inner surface of the plasma membrane which buds into the cell to form a coated vesicle

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19
Q

What is dynamin?

A

Dynamin is a GTPase

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20
Q

What does Dynamin do?

A

Binds to a forming Clathrin bud forming a helical collar. GTP hydrolysis couples with vesicle scission and Dynamin lengthen popping the vesicle of the parent membrane

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21
Q

What are the presynaptic events at a chemical synapse?

A

AP travels via axon to presynaptic nerve terminal. Opening VG Ca channels. Ca influx triggers exocytotic machine causing neurotransmitter release.

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22
Q

What is botulinum toxin?

A

A neurotoxin released by Clostridium Botulinum bacteria found in 8 different types with a heavy and light chain structure

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23
Q

What does botulinum toxin do?

A

Blocks acetylcholine release at the neurotransmitter causing muscle paralysis, Botulinum A effects can last up to three months

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24
Q

What is Botulinum toxin A used for?

A

Has been FDA approved to be used as botox

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25
how does Botulinum A block receptors?
Heavy chain binds selectively and irreversibly to presynaptic cholinergic receptors and toxin is exocytosis, the light chain is released and binds to and cleaves SNAP25 and Synaptobrevin preventing exocytosis
26
What does tetanus effect?
Tetanus is taken up by the motor neuron and blocks the inhibitory neuron at the neuromuscular junction causing overexcitations of the excitatory neuron meaning over release and muscle spasm (Tetanus). It cleaves Synaptobrevin inactivating the inhibitory neuron.
27
What is the difference between botulinum toxin and tetanus?
Botulinum toxin effects SNAP 25 and Synaptobrevin and causes flaccid paralysis, Tetanus affects just Synaptobrevin and causes spastic paralysis
28
What does alpha-latrotoxin do?
it bind Neurexins
29
What are neurexins?
Neurexins are a group of 2000 proteins involved with aligning cells
30
How alpha-latrotoxin bind neurexins?
It forms a dimer with neurexin which creates an ungated calcium channel. This phosphorylates snare proteins which activates phospholipase C, mobilizing intracellular Ca stores causing uncontrolled Neurotransmitter release from SSV.
31
What is synapsin?
A phosphoprotein found at all synapses. Has three distinct SYN genes (1,2 and 3) and multiple isoforms.
32
What does Synapsin Do?
It is associated with the cytosolic face of SSV's and controls synaptic vesicle motility and exocytosis. it binds actin and when phosphorylated by CaMKII it releases bonds making vesicles avaliable
33
What are reserve pool vesicles anchored to the cytoskeleton by?
Synapsin
34
When synapsin is KO from the body what conditions can arise?
Epilepsy, Schizophrenia and learning disabilities resulting from less synapsin present or reduced phosphorylation
35
What controls neurotransmitter responses?
Available receptors on the post synaptic cell
36
What forms can neurotransmitters take?
excitatory, inhibitory or modulatory
37
What are the four classes of Neurotransmitters?
Type 1:Amino acids (Classical), Type 2: Amines and Purines, Type 3: Neuropeptides and Type 4: Gases
38
What are the properties of Type 1 neurotransmitters?
Found in small synaptic vesicles, include Glutamate (Inhibitory) and GABA + Glycine (Excitatory).
39
What are the properties of Type 2 neurotransmitters?
Found in SSV's, include Acetylcholine, Catecholines (Noradrenaline and dopamine), histamine and serotonin
40
What are the properties of Type 3 Neurotransmitters?
Found in LDCV's include Opioids, Neuropeptide Y and Substance P
41
What are the properties of Type 4 Neurotransmitters?
Cannot be contained in lipid vesicles and include NO and CO
42
What are the Criteria for neurotransmitters?
1. must be present in the brain, neurons, 2. present in synaptic vesicles, 3.the enzymes for synthesis must exist in the presynaptic terminal or in the cell body, 4.released in response to nerve terminal depolarization, 5.specific receptors must exist on the postsynaptic membrane, 6. Action must be mimicked or inhibited by pharmacological agents, 7. there must be uptake mechanisms and metabolizing agents
43
What type of neurotransmitter is dopamine?
A type 2, catecholine
44
What are exceptions to the neurotransmitter rules?
Glutamate which can be made by astrocytes and NO and CO which aren't present in synaptic vesicles
45
What is dopamine known to be involved in?
Regulation of movement, attention, mood, cognition, addiction and reward
46
What is Parkinson's disease?
Neurological condition that effects movement and coordination, onset is typically 55-65 and first signs are often weakness or tremors. Neurons of the Substantia Nigra degenerate
47
What causes loss of cells in the Substantia Nigra?
alpha-synuclein
48
What is alpha-synuclein?
Found in Lewy bodies, forms toxic aggregates, some forms of familial Parkinson's have a-synuclein mutations.
49
What is alpha-synuclein involved in?
mitophagy, autophagy, inflammation, ER-Golgi transport, synaptic vesicles, mitochondria, lysosomes and other proteolytic machinery
50
How is a-synuclein involved in Dopamine release?
Regulates dopamine release- involved in synaptic vesicle exocytosis, SNARE complex formation, Senses curved membrane.
51
What are the enzymes required for Dopamine synthesis?
Tyrosine -> Tyrosine Hydroxylase ->L-Dopa -> Dopamine ->Norepinephrine ->Epinephrine
52
What protein carries dopamine?
VMAT - Vesicular monoamine transportor
53
What two receptors does dopamine have?
Presynaptic dopamine receptors and Extra synaptic dopamine receptors
54
What receptor type are dopamine receptors?
G-protein coupled receptors (trimeric GTP-binding, dissociate into two components and are slow acting
55
What two mimics or antagonists does dopamine have?
Dopamine receptor agonist and Dopamine receptor antagonists
56
What are dopamine receptor agonists?
Bromocriptine (Parlodel) - Treats Parkinson's and stimulate nerves to control movement
57
What are dopamine receptor antagonists?
Haloperidol - Antipsychotics, treats schizophrenia, bi-polar and stimulant indued psychosis
58
What is L-dopa treatment?
can cross Blood brain barrier and be converted to dopamine, can only occur in remain neurons cant revers degeneration, prolonged treatment often has side effects (psychosis and dyskinesia)
59
What is the process of dopamine uptake and metabolism?
Synthesis via tyrosine hydroxylase, Loaded into vesicles (VMAT), exocytosis + binding, Re-uptake by Dopamine transporters (DAT), degradations via monoamine oxidase, recycled or further processed.
60
What stimulants inhibit Dopamine reuptake?
Cocaine and amphetamines (Causing euphoria and wakefulness)
61
Where are dopamine receptors found in the brain?
substantia nigra- striatum circuit, Ventral segmental area (VGT) to Nucleus accumbus, Frontal cortex and limbic system
62
Which stimulant enhances dopamine release?
heroin

Neur 201 (2 decks)

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