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Biology of the mind > Neurotransmitters > Flashcards

Neurotransmitters Flashcards

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1
Q

Where can neurotransmitter receptors be found? (3)

A

Neurones
Muscles
Glands

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2
Q

Why is diversity in receptor location on neurones important? (1)

A

Allows for complex modulation

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3
Q

What are the three different synaptic targets on neurones? (3)

A

Axodendritic
Axosomatic
Axoaxonic

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4
Q

What are the three different types of neurotransmitters? (3)

A

Excitatory
Inhibitory
Modulatory

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5
Q

What are autoreceptors and where can they be found? (4)

A

Found on post synaptic terminal
Can also be found on pre synaptic terminal
Detect neurotransmitter the neurone released
Inhibit pre synaptic terminal - typically reduce further release of synthesis of neurotransmitter

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6
Q

What type of neurotransmitter is acetylcholine and where is it released? (2)

A

Excitatory neurotransmitter
Released at skeletal neuromuscular junction

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7
Q

Which muscles respond to acetylcholine? (1)

A

Skeletal muscles

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8
Q

Which neurotransmitter does the autonomic nervous system use? (2)

A

Acetylcholine
Noradrenaline

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9
Q

What are glands? (2)

A

Group of cells that secrete hormones and can be stimulated to do so by neurotransmitters

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10
Q

Which receptor connects the nervous system to the endocrine system? (1)

A

Neuroendocrine synapse

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11
Q

What are the two different types of neurotransmitter receptors? (2)

A

Ionotropic
Metabotropic

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12
Q

Difference between ionotropic and metabotropic

A

Ionotropic:
Fast response
Short-lived response
Direct effect on post synaptic cell
Ligand-gated
Ion selectivity filter

Metabotropic:
Slow response
Long-lived response
Indirect effect

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13
Q

How do ionotropic receptors work? (4)

A

Neurotransmitter binds to the receptor
Channel opens
Ion flow across membrane
Post synaptic response may be excitatory or inhibitory

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14
Q

What is an ion selectivity filter and where is it found? (3)

A

Only allows certain ions to pass through channels
Often permeable to cations/anions
In ionotropic receptors

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15
Q

How do ionotropics get diversity? (2)

A

Subunits provide diversity due to unique functional and pharmacological properties

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16
Q

What is an excitatory post synaptic response? (3)

A

Ions enter
Inside becomes more positive than outside
more likely to reach threshold and generate action potential

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17
Q

What is an inhibitory post synaptic response? (3)

A

Ions enter
Inside more negative than outside
Less likely to reach threshold and less likely to generate action potential

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18
Q

How do metabotropic receptors work? (4)

A

G-protein coupled receptors
Have a neurotransmitter binding cite and G-protein binding site
Can provide excitatory or inhibitory effects on G-protein gated ion channels or enzymes that produce second messengers (calcium, cAMP etc)

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19
Q

What are G-proteins? (1)

A

Guanine nucleotide-binding proteins

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20
Q

How do G-proteins work? (7)

A

GDP binds to alpha subunit of G-protein
Neurotransmitter binds to receptor
GDP converted to GTP - phosphate group added
Alpha subunit detaches
G-protein switched on
Downstream response by alpha subunit/beta-gamma subunit
G-proteins are GTPases so hydrolyse GTP back to GDP by themself

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21
Q

What are the downstream responses by alpha subunit/beta-gamma subunit? (4)

A

Ion channels - activated G-proteins can act on G protein gated ion channels

Enzymes - activated G-proteins can act on enzymes that regulate the production of second messengers

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22
Q

What are the two different types of G-proteins that can modulate cAMP (second messenger)? (2)

A

Gs - stimulatory
Gi - inhibitory

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23
Q

What does phosphorylation of transcription factor CREB do? (3)

A

Alters gene expression, and is implicated in learning, memory, addiction, anxiety etc

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24
Q

Which G-protein activates the enzyme phospholipase? (1)

A

Gq

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25
Q

How is acetylcholine synthesised? (2)

A

Synthesised from acetyl coA and choline by choline transferase (ChAT)

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26
Q

What is ChAT? (1)

A

A marker for cholinergic neurones

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27
Q

How is acetylcholine metabolised? (1)

A

Metabolised in synaptic cleft by acetylcholinesterase

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28
Q

Role of acetylcholine (3)

A

In somatic nervous system - lower motor neurones
Autonomic system - all preganglionic cells + postganglionic in the parasympathetic division are cholinergic
Central - cholinergic cell bodies located in 2 key places: the basal forebrain and the brainstem.

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29
Q

What are the two acetylcholine receptors? (2)

A

Nicotonic receptors - sensitive to nicotine
Muscarine receptors - sensitive to muscarine

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30
Q

What are nicotinic receptors? (4)

A

Non-selective cation channel
Made up of 5 subunits
Expressed on skeletal muscle at the neuromuscular junction – lead to muscle contraction
Nicotinic receptors on postganglionic neurons of both divisions

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31
Q

What are muscarinic receptors? (2)

A

Odd numbers (M1, M3, M5) –
Gq coupled - (produces DAG and IP3 –> Ca2+ released from stores)
Even numbers (M2, M4) –
Gi coupled, inhibitory effect on cAMP levels
mAchRs also expressed at the neuromuscular junction but on the presynaptic terminal - can modulate acetylcholine release from the lower motor neuron
mAchRs expressed on tissue innervated by postganglionic neurons of parasympathetic division

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32
Q

Rate of expression of acetylcholine receptors in the brain (1)

A

Muscarinic acetylcholine receptors have a higher rate of expression in the brain than nicotinic receptors

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33
Q

How is glutamate synthesised? (1)

A

Synthesised from glutamine by glutaminase

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34
Q

How is glutamate metabolised? (2)

A

Not broken down in the cleft – reuptake by neurons or glia by transporters
Broken down in glia into glutamine by glutamine synthetase, recycled

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35
Q

What are ionotropic glutamate receptors? (3)

A

Named after agonists.
All are tetramers (made up of 4 subunits but lots of diversity in subunits)
All may be permeable to Na+, Ca2+ and K+ to different degrees and depending on subunits presen

35
Q

Where can glutamate be found? (1)

A

Glutamatergic sensory neurons - cell bodies form dorsal root ganglia
Glutamatergic cells in the dorsal horn of the spinal cord
Large density of glutamatergic neurons in the cortex, hippocampus, amygdala, and brainstem

36
Q

What are AMPA receptors? (2)

A

Responsible for fast, excitatory transmission in the CNS

37
Q

What are NMDA receptors? (3)

A

Coincidence receptors - both ligand gated and voltage gated and need a co-receptor
Depolarises membrane to remove the Mg2+ block on NMDA-Rs
Allows NMDA receptors to open if glutamate + glycine (co-agonist) bound

38
Q

NMDA receptors as calcium channels (2)

A

Once all conditions met: ion channel allows Ca2+ and Na+ to enter (most more permeable to the former) and K+ to leave.

39
Q

Why are NMDA receptors as calcium channels important? (2)

A

Excitatory but calcium also acts as a second messenger
Has an effect on gene transcription, growth proteins, insertion of AMPA receptors etc.

40
Q

What is memantine? (1)

A

NMDA-R antagonist - prevents intracellular damage

41
Q

What are kainite receptors? (1)

A

Permeable to Na+ and K+ (may have some Ca2+ permeability too depending on subunits).

42
Q

What are metabotropic glutamate receptors? (2)

A

mGluRs play a modulatory role in plasticity and regulation of excitotoxicity (excess glutamate)

43
Q

What are the 3 classes of mGluRs? (3)

A

Class I (Gq coupled), mGluR1/5
Class II (Gi coupled), mGluR2/3
Class III (Gi coupled), mGluR4,6-8

44
Q

How is GABA synthesised? (2)

A

Synthesised from glutamate via glutamic acid decarboxylase (GAD)

45
Q

How is GABA metabolised? (2)

A

Reuptake by neuron or glia. Glia can break down GABA –> glutamate (via GABA-transaminase/GABA-T) then into glutamine (by GS).

46
Q

What is the most abundant inhibitory neurotransmitter? (1)

A

GABA

47
Q

What is a seizure? (1)

A

Excessive or synchronous neuronal activity

48
Q

What is epilepsy? (1)

A

A neurological disorder, one possible cause of recurrent seizures

49
Q

What can be used to detect a seizure? (1)

A

EEG

50
Q

What are GABA A receptors? (2)

A

Pentamers (made up of 5 subunits), permeable to Cl- channel
Huge diversity in subunits

51
Q

How can GABA be depolarising? (3)

A

In development GABA can be excitatory
Immature neurones have high concentration of Cl- ions
When GABA binds to receptors Cl- leaves the cell

52
Q

What are metabotropic GABA B receptors? (2)

A

Gi coupled – open ion channels (such as GIRKs), reduces cAMP through adenylyl cyclase inhibition

53
Q

What is Baclofen and what can it be used to treat? (2)

A

Baclofen is a selective agonist of GABAB-Rs
Used to treat muscle spasticity through CNS action.

54
Q

What are glycine receptors? (2)

A

Glycine receptors are pentamers (5 subunits) surrounding a Cl- channel, just like GABAA (but not as diverse)

55
Q

Where is glycine found? (2)

A

Commonly found in spinal cord, brainstem, and retina (on right)
Like GABA, depolarising in development

56
Q

How is dopamine synthesised? (1)

A

Synthesised via tyrosine hydroxlase (TH) then DOPA decarboxylase (DDC/AADC)

57
Q

How is dopamine metabolised? (2)

A

Reuptake then metabolised into DOPAC by monoamine oxidase (MAO)
Can also be metabolised by the enzyme COMT

58
Q

What type of receptors are dopamine receptors? (1)

A

Metabotropic

59
Q

What are the dopamine receptors? (4)

A

Gs or Gi coupled – former activates enzyme adenylyl cyclase (AC), latter inhibits – stimulatory or inhibitor
Gs = D1-like family: D1, D5
Gi = D2-like family: D2, D3, D4

60
Q

Describe the functions of dopamine (6)

A

Role in motor function and control, reward & addiction, motivation, cognition, memory, emotion/mood etc

61
Q

Where is dopamine produced? (2)

A

Major nuclei in the substantia nigra and the ventral tegmental area (both parts of the midbrain).

62
Q

What role does dopamine play in peripheral function (2)

A

D1 receptor expressed in kidney
Involved in the sympathetic nervous system e.g. release at the kidney

63
Q

What role does noradrenaline play in the brain? (3)

A

In the brain, role in cognition, emotion etc.
Locus coeruleus is the main location in the brain of noradrenergic neurons
Norepinephrine released by postganglionic neurons in the sympathetic division.

64
Q

What are adrenergic receptors? (3)

A

Different affinity for norepinephrine or epinephrine

Alpha-1 (Gq) and beta (Gs) are excitatory
Alpha-2 (Gi) inhibitory - often presynaptic

65
Q

What is serotonin (5-HT) and how is it synthesised? (2)

A

5-HT is an indoleamine synthesised from tryptophan (via 5-HTP)
Tryptophan hydroxylase (TPH) converts tryptophan into 5-HTP then 5-HTP converted to 5-HT by aromatic amino acid decarboxylase (AADC).

66
Q

How is serotonin? (2)

A

Metabolism following reuptake via monoamine oxidase (MAO) into 5-HIAA

67
Q

What type of receptor is 5-HT3 receptor? (1)

A

Ionotropic

68
Q

What is 5-HT3 receptor? (2)

A

Pentameric, non-selective cation channel
5-HT1(A-F)/5: Gi (often presynaptic) - can activate GIRK channels
5-HT4,6,7: Gs
5-HT2(A-C): Gq - increases IP3

69
Q

Describe the functions of serotonin and where is it found (2)

A

In the CNS, serotonergic cell bodies contained in the raphe nuclei (brainstem).

Projections to numerous brain regions including the ventromedial PFC

Serotonin plays a role in mood, emotion, cognition, thermoregulation

70
Q

What are the peripheral functions of serotonin? (2)

A

Some well-known central functions of 5-HT (mood, appetite, etc.) are influenced by the gut-brain axis

Range of peripheral effects:
- insulin secretion
- modulate glucose level
- effect on skeletal muscle and storage of fat in fat cells

71
Q

What are SSRIs? (3)

A

Selective serotonin reuptake inhibitors (SSRIs) block serotonin transporters (SERT) - though some efficacy to norepinephrine and/or dopamine transporters

72
Q

What is therapeutic lag? (1)

A

Time lag in therapeutic response to antidepressant medication

73
Q

What are peptides? (2)

A

Chains of amino acids (usually 3 to 36 amino acids long) linked by peptide bonds
Begin with an amino group (NH3) and terminate with a carboxyl group (COOH).

74
Q

How are peptides synthesised? (2)

A

After synthesis in the soma, peptides are cleaved and packaged into “secretory granules”, where they are transported towards the terminal.

Once there, stored in large dense-core vesicles (as opposed to small, clear-core vesicles)

75
Q

How are peptides released? (2)

A

Co-transmission – peptides and small molecule transmitters released - usually separate synaptic vesicles

Peptides can be released extrasynaptically (away from synaptic cleft) and often require high-frequency stimulation to trigger release

76
Q

What is volume transmission? (2)

A

Occurs where peptides diffuse over a long distance to reach remote targets

76
Q

What type of receptors are peptide receptors? (2)

A

All peptide receptors are G-protein coupled (metabotropic), adding to their slow, modulatory characteristics

77
Q

What are endorphins? (2)

A

Are endogenous opioids that control pain, immune responses, and other body functions

77
Q

What receptors do endogenous opioids act on and what are the effects?(2)

A

Act on various opioid receptors (mu, delta, kappa, and nociception/ORL1)
Range of effects including euphoria, sedation, analgesia, respiratory and cardiac depression, dependence, etc

78
Q

What is a migraine? (4)

A

Neurological disorder
Strong genetic link
Headache pain that lasts for a number of days
Nausea and vomiting

79
Q

How is migraine prevented? (2)

A

Includes tricyclic antidepressants, beta blockers, anticonvulsants

79
Q

How is migraine managed? (2)

A

Includes analgesics, CGRP receptor antagonists, triptans

80
Q

What are Triptans? (2)

A

Triptans are agonists for 5-HT1B/1D receptors – indirectly inhibits CGRP release
CGRP receptors can be targeted directly with antagonists or antibodies

81
Q

Describe metabolism of peptides (3)

A

Broken down into inactive amino acid fragments by peptidases (bound to the extracellular surface of the membrane).

Some evidence of a reuptake system for some peptides (cholecystokinin).

82
Q
A

Biology of the mind (9 decks)

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