Neuromodulation

Question 1

Name 4 diffuse modulatory systems

Answer 1

dopamine
serotonin
noradrenaline
acetylcholine

Question 2

Describe the features of an ionotropic receptor

Answer 2

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

Question 3

Describe the features of a metabotropic receptor

Answer 3

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

Question 4

Describe the activation of metabotropic receptors

Answer 4

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

Question 5

Describe the cascade of signal transduction to a metabotropic receptor

Answer 5

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

Question 6

Describe the process of G protein uncoupling

Answer 6

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

Question 7

What are the two G protein coupled effector systems?

Answer 7

a subunits - around 20

bg complexes - 5b and 12g

Question 8

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

Answer 8

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

Question 9

What do the bg complexes of?

Answer 9

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

Question 10

What is the function of phosphatases?

Answer 10

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

Question 11

What do presynaptic receptors do?

Answer 11

change the amount of neurotransmitter released

Question 12

How are G protein signals amplified?

Answer 12

one transmitter bound receptor can uncouple multiple G proteins

Question 13

What do auto receptors do?

Answer 13

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

Question 14

What do heteroreceptors do?

Answer 14

axoaxonic synapses or extrasynaptics modulate the release of another transmitter

Question 15

What do postsynaptic receptors do?

Answer 15

change the firing pattern or activity of a neurotransmitter

Question 16

How do postsynaptic receptors firstly change firing rate?

Answer 16

by acting on the ligand gated channels

Question 17

How do postsynaptic receptors indirectly change firing rate?

Answer 17

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

Question 18

Name the types of presynaptic receptor

Answer 18

autoreceptors

heteroreceptors

Question 19

Name the types of metabotropic receptor

Answer 19

metabotropic glutamate
GABAb
muscarinic acetylcholine
dopamine
noradrenergic
adrenergic
serotonin
neuropeptide

Question 20

Describe the synthesis of neuropeptides

Answer 20

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

Question 21

How are hippocampal theta waves controlled?

Answer 21

by the neuromodulatory acetylcholine release in the hippocampus

Question 22

What is the function of scopolamine?

Answer 22

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

Question 23

Name two agonists of the opioidergic system

Answer 23

morphine and heroin

Question 24

Name two antagonists of the opioidergic system

Answer 24

naloxone and nalteroxe

Question 25

What are the roles of the opioidergic system?

Answer 25

analgesia; release of endogenous opioids inhibits pain signals
relaxation; regulates noradrenaline release

Question 26

What are some subjective effects of opiate use?

Answer 26

euphoria and intense rush; heroin due to route of administration
tolerance/dependence; increasing doses required for analgesic response

Question 27

What does sustained release of noradrenaline cause?

Answer 27

activation of the autonomic nervous system

Question 28

What causes tolerance to opiates?

Answer 28

chronic activation of the opioid receptors

Question 29

What does acute morphine do?

Answer 29

acutely inhibits firing of LC neurons through the Gi pathway

Question 30

What does chronic treatment of opioids cause?

Answer 30

locus coerleus neurons return to their normal firing rates

Gs pathway up regulates to match Gi

Question 31

What does opioid withdrawal cause?

Answer 31

dramatic increase in locus coerleus firing (in absence of Gi inhibition, Gs is hypersensitive)

Question 32

What is cAMP?

Answer 32

cyclic adenosine monophosphate; a second messenger

Question 33

What does protein kinase A (PKA) do?

Answer 33

activates the Na+ channel and depolarises the neuron

Question 34

How does the Gs pathway affect the second messenger cascade?

Answer 34

it increases PKA and depolarises the neuron

Question 35

How does the Gi pathway affect the second messenger system?

Answer 35

decreases PKA and inhibits the neuron

Question 36

What do the Gbg subunit on Gi do?

Answer 36

activates the K+ channel causing more inhibition

Question 37

What compensatory changes take place in the up regulation of the cAMP pathway?

Answer 37

increased expression of adenylyl cyclases
increased PKA expression
decreased PKA degradation