Neuromodulation Flashcards

1
Q

Name 4 diffuse modulatory systems

A

dopamine
serotonin
noradrenaline
acetylcholine

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2
Q

Describe the features of an ionotropic receptor

A
ligand gated ion channels
direct transmission
flux ions directly
excitatory or inhibitory
fast transmission
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3
Q

Describe the features of a metabotropic receptor

A

signals not sent directly but through G coupled proteins which trigger a series of intracellular events
indirectly lead to ion flux
slower but prolonged information transmission
hundreds of G protein coupled receptor

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4
Q

Describe the activation of metabotropic receptors

A

transmitter binds to extracellular domain of receptor
change in intracellular domain
binding triggers G protein uncoupling
signal is transducer across the cell membrane

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5
Q

Describe the cascade of signal transduction to a metabotropic receptor

A
G protein
effector protein
second messenger
kinase enzyme
channel activation/gene transcription
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6
Q

Describe the process of G protein uncoupling

A

at rest G protein is bound to GDP
on the binding of the ligand to the receptor GDP is switched for GTP
the G protein splits
the parts diffuse separately
individually stimulate activity of other effector proteins
the recomplexes to repeat the cycle

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7
Q

What are the two G protein coupled effector systems?

A

a subunits - around 20

bg complexes - 5b and 12g

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8
Q

What are the types of G protein a subunits and what do they do?

A

Gs; stimulates adenylyl cyclase
Gi; inhibits adenylyl cyclase
Gg; stimulates phospholipase C

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9
Q

What do the bg complexes of?

A

activate K+ channels directly via the G protein gates ion channel

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10
Q

What is the function of phosphatases?

A

to regulate and maintain the activity of proteins, phosphorylation gated channels open and close dependent on phosphorylation

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11
Q

What do presynaptic receptors do?

A

change the amount of neurotransmitter released

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12
Q

How are G protein signals amplified?

A

one transmitter bound receptor can uncouple multiple G proteins

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13
Q

What do auto receptors do?

A

regulate the release of transmitter by modulating its synthesis, storage or reuptake

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14
Q

What do heteroreceptors do?

A

axoaxonic synapses or extrasynaptics modulate the release of another transmitter

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15
Q

What do postsynaptic receptors do?

A

change the firing pattern or activity of a neurotransmitter

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16
Q

How do postsynaptic receptors firstly change firing rate?

A

by acting on the ligand gated channels

17
Q

How do postsynaptic receptors indirectly change firing rate?

A

by activating metabotropic receptors leading to G protein gated or phosphorylation gated channels opening

18
Q

Name the types of presynaptic receptor

A

autoreceptors

heteroreceptors

19
Q

Name the types of metabotropic receptor

A
metabotropic glutamate
GABAb
muscarinic acetylcholine
dopamine
noradrenergic
adrenergic
serotonin
neuropeptide
20
Q

Describe the synthesis of neuropeptides

A
gene transcribed from mRNA
translated to protein
transported though golgi to vesicles
chopped into neuropeptides
multiple neuropeptides can be synthesised from propeptides
21
Q

How are hippocampal theta waves controlled?

A

by the neuromodulatory acetylcholine release in the hippocampus

22
Q

What is the function of scopolamine?

A

its an antagonist of muscarinic acetylcholine receptors
disrupts hippocampal theta waves
disrupts learning and memory

23
Q

Name two agonists of the opioidergic system

A

morphine and heroin

24
Q

Name two antagonists of the opioidergic system

A

naloxone and nalteroxe

25
What are the roles of the opioidergic system?
analgesia; release of endogenous opioids inhibits pain signals relaxation; regulates noradrenaline release
26
What are some subjective effects of opiate use?
euphoria and intense rush; heroin due to route of administration tolerance/dependence; increasing doses required for analgesic response
27
What does sustained release of noradrenaline cause?
activation of the autonomic nervous system
28
What causes tolerance to opiates?
chronic activation of the opioid receptors
29
What does acute morphine do?
acutely inhibits firing of LC neurons through the Gi pathway
30
What does chronic treatment of opioids cause?
locus coerleus neurons return to their normal firing rates | Gs pathway up regulates to match Gi
31
What does opioid withdrawal cause?
dramatic increase in locus coerleus firing (in absence of Gi inhibition, Gs is hypersensitive)
32
What is cAMP?
cyclic adenosine monophosphate; a second messenger
33
What does protein kinase A (PKA) do?
activates the Na+ channel and depolarises the neuron
34
How does the Gs pathway affect the second messenger cascade?
it increases PKA and depolarises the neuron
35
How does the Gi pathway affect the second messenger system?
decreases PKA and inhibits the neuron
36
What do the Gbg subunit on Gi do?
activates the K+ channel causing more inhibition
37
What compensatory changes take place in the up regulation of the cAMP pathway?
increased expression of adenylyl cyclases increased PKA expression decreased PKA degradation