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Module 202 Neuroscience & behaviour > T1 L6 Chemicals in the brain > Flashcards

T1 L6 Chemicals in the brain Flashcards

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1
Q

How is the pool of vesicles above the active zone anchored to the cytoskeleton?

A

By synapsin

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2
Q

What activates calcium calmodulin activated kinase II?

A

Calcium ions

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3
Q

What does calcium calmodulin activated kinase II do?

A

Phosphorylates synapsin

P-synapsin can no longer bind to the cytoskeleton so vesicles dock to the active zone

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4
Q

What does the SNARE complex do?

A

It docks vesicles to the plasma membrane at the active zone

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5
Q

Describe the 4 steps of exocytosis during neurotransmitter release

A

1) Vesicle docks
2) SNARE complexe form to pull membranes together
3) Entering calcium binds to synaptotagmin
4) Calcium-bound synaptotagmin catalyses membrane fusion by binding to SNAREs and the plasma membrane

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6
Q

What does the botulinum toxin do?

A

Decreases neuromuscular transmission of acetylcholine

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7
Q

Where does botox come from?

A

Clostridium botulinum

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8
Q

Where do tetanus toxins come from?

A

Clostridium Tetani

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9
Q

What does botox do?

A

Acts directly at neuromuscular junction

Muscles lose all input so become permanently relaxed

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10
Q

What does the tetanus toxin do?

A

Inhibits the release of Glycine and GABA at inhibitory neurons
Results in dis-inhibition of cholinergic neutrons
Causes permanent muscle contraction

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11
Q

What diseases affect the presynaptic terminal?

A 
Congenital myasthenic syndromes
LEMS
Cognitive disorders
Botulinum & tetanus toxins
Latrotoxin
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12
Q

How does LEMS affect the presynaptic terminal?

A

Attacks presynaptic calcium channels

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13
Q

How does congenital myasthenic syndrome affect the presynaptic terminal?

A

Results in impaired vesicle recycling

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14
Q

How does latrotoxin affect the presynaptic terminal?

A

Triggers vesicle fusion

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15
Q

How do cognitive disorders affect the presynaptic terminal?

A

They impair transsynaptic signalling

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16
Q

How are vesicular transporters powered by proton gradients?

A

ATPase proton pump loads up vesicles with H+

Makes vesicles acidic

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17
Q

How are plasma membrane transporters powered by electrochemical gradients?

A

Na concentration is higher outside & K is higher inside

Glutamate is cotransported with 2 Na+

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18
Q

What are astrocytes?

A

A type of glial cell with extensions that wrap around the gaps or synapses between neurons

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19
Q

What are the categories of neurotransmitters?

A

Amino acids
Monoamines
Acetylcholine
Neuropeptides

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20
Q

Where are neuropeptides synthesised?

A

In the cell soma & transported to the terminal

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21
Q

Where are neuropeptides stored?

A

In secretory granules

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22
Q

What stimulates a release of neuropeptides?

A

A global increase in calcium ions

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23
Q

Where are amino acids, monoamines & acetylcholine synthesised & stored?

A

Synthesised locally in presynaptic terminal

Stored in synaptic vesicles

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24
Q

What stimulates a release of amino acids, monoamines or acetylcholine?

A

A local increase in calcium ions

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25
Give an example of a fast neurotransmitter
Amino acids
26
Give an example of a slow neurotransmitter
Neuropeptides
27
What is a fast neurotransmitter?
Stored in synaptic vesicles docked close to a voltage-gated calcium channels in membrane of nerve terminal Released in short burst when membrane is depolarised
28
What is a slow neurotransmitter?
Stored in separate vesicles further from the membrane | Release is slower as they have to migrate first to the membrane & only occurs when calcium builds up sufficiently
29
Give an example of an excitatory amino acid transmitter?
Glutamate in the CNS | Slightly depolarises postsynaptic cell's membrane
30
Give an example of an inhibitory amino acid transmitter?
GABA in the brain Glycine in the spinal cord & brainstem Slightly hyperpolarises postsynaptic cell's membrane
31
Give an example of a modulatory system
Serotonergic system
32
What is modulation?
Affects large neural networks, cortex, spinal cord, cerebellum Changes how likely these areas are to be excited
33
What are some functions of the serotonergic system?
``` Mood Sleep Pain Emotion Appetite ```
34
What are the 2 ways glutamate is synthesised?
From glucose via the Krebs cycle | From glutamine converted by glutamine into glutamate
35
What do vesicular glutamate transporters do?
Load & store glutamate into vesicles
36
How is glutamate taken back up?
By excitatory amino acid transporters in the plasma membrane of presynaptic cell & surrounding glia
37
How is glutamate converted to glutamine?
By glial cells | Glutamine then transported from the glia back to nerve terminals where it is converted back into glutamate
38
How is GABA synthesised?
From glutamate in a reaction catalysed by glutamic acid decarboxylase
39
What do vesicular GABA transporters do?
Load & store GABA into vesicles | Gly also uses this transporter
40
How is GABA cleared from the synapse?
By reuptake using transporters on glia & neutrons including non-GABAergic neurons
41
What happens if there is too much Glu or too little GABA?
Hyper excitability Epilepsy Excitotoxicity
42
What happens if there is too much GABA?
Sedation / coma
43
What happens in cerebral ischaemia?
Metabolic events that retain electrical gradient are abolished Reversal of Na/K gradient Transporters release glutamate from cells by reverse operation Excitotoxic cell death
44
What happens with GHB (date-rape drug)?
GABA metabolite that is converted back to GABA Increases amount of available GABA Too much leads to unconsciousness & coma
45
What are the 2 types of monoamines?
Catecholamines | Indolamines
46
Give some examples of catecholamines
Dopamine Epinephrine Norepinephrine
47
Give an example of an indolamine
Serotonin
48
Describe the path of dopamine synthesis
Tyrosine --> dopa --> dopamine --> NE --> epinephrine
49
What do vesicular monoamine transporters do?
Load catecholamines into vesicles for storages
50
What does L-DOPA (Levodopa) do?
Precursor of dopamine Used to treat Parkinson's disease Dopa decarboxylase converts it into dopamine increasing the pool of releasable transmitter
51
How is catecholamine released?
By calcium dependent exocytosis
52
What happens once catecholamine is released?
It binds and activates the receptor
53
How is the signal for catecholamine release terminated?
By reuptake into the axon terminal by transporters powered by the electrochemical gradient. Dopamine transporters, norepinephrine transporters
54
What happens to catecholamines in the cytoplasm?
They are reloaded back into vesicles Enzymatically degraded by monoamine oxidases (MAOs) Inactivated by catechol-O-methyl-transferase (COMT)
55
What effect does amphetamine have on catecholamine?
Reverse transporter so pumps out transmitter & blocks uptake (DA & NE)
56
What effect does cocaine & methylphenidate have on catecholamine?
(Ritalin) block DA reuptake into terminals | More DA in synaptic cleft - extended action on postsynaptic neuron
57
What effect does selegiline have on catecholamine?
MAO inhibitor found in dopaminergic nerve terminals Prevents degradation of DA allowing more to be released on subsequent activations Used to treat early-stage PD, depression & dementia
58
What effect does entacopone have on catecholamine?
COMT inhibitor | Treatment of PD
59
How is serotonin synthesised?
Tryptophan --> 5-hydroxytryptophan --> serotonin
60
Describe serotonin storage, release & reuptake
Stored in vesicles Signal terminated by reuptake by serotonin transporters on presynaptic membrane Destroyed by MAOs in the cytoplasm
61
What drugs module the release and reuptake of serotonin?
Fluoxetine Fenfluramine MDMA
62
How does fluoxetine (prozac) affect serotonin?
Blocks reuptake of serotonin SSRI - selective serotonin reuptake inhibitor Treatment of depression & OCD
63
How does fenfluramine affect serotonin?
Stimulates the release of serotonin & inhibits its reuptake Has been used as an appetite suppressant in the treatment of obesity
64
How does MDMA affect serotonin?
(Ecstasy) causes NE & serotonin transporters to run backwards released neurotransmitter into synapse / extracellular space
65
Describe the synthesis of acetylcholine
Choline acetyltransferase converts choline & acetyl CoA into acetylcholine
66
What is the function of vesicular acetylcholine transporter?
Packages acetylcholine into vesicles
67
What does acetylcholinesterase do?
Rapidly degrades acetylcholine in the synaptic cleft. | Choline is then transported back into the presynaptic terminal & converted to acetylcholine
68
Describe the synthesis & secretion of acetylcholinesterase
Made by cholinergic neuron | Secreted into synaptic cleft & associated with axonal membrane
69
What do acetylcholinesterase inhibitors do?
Block the breakdown of acetylcholine which prolongs its actions in the synaptic cleft
70
Give an example of an acetylcholinesterase inhibitor
Neostigmine
71
Describe the properties of neuropeptides
Slow transmission Vary in their methods of synthesis & release from small molecule transmitters Short polypeptide chains 3-36 amino acids Over 100 neuropeptides described
72
Describe the process of neuropeptide release & degradation
Follow secretory pathway Not released in same way as small molecule transmitters 1) Dense core vesicle fusion & exocytosis occurs due to global elevations of Ca2+ 2) Neuropeptide vesicle membrane is recycled but not refilled 3) Bind to & activate receptor 4) Neuropeptide signalling is terminated by diffusion from site of release & degradation. by proteases in extracellular environment 5) Release is slower than small molecule release & signals may be maintained for longer
73
Describe what happens to nitric oxide
1) Nitric oxide is made in postsynaptic neuron by nitric oxide synthase 2) Gas rapidly diffuses from its site of synthesis 3) Activates guanylyl cyclase which makes cGMP 4) Within a few sec of being produced, NO is converted to biologically inactive compound 5) Potentially useful for coordinating activities of multiple cells in a small region
74
How is nitric oxide synthase activated?
By the binding of Ca2+ & calmodulin
75
What are endocannabinoids?
Small lipids which mostly cause reduced GABA release at certain inhibitory terminals

Module 202 Neuroscience & behaviour (39 decks)

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