Adrenergic and serotonergic synapses

Question 1

Which receptors work on a faster timescale, GABARs/iGluRs or DA/5-HT receptors?

Answer 1

GABARs/iGluRs

Question 2

How are NTs released in NA/5-HT synapses?

Answer 2

Via a varicosity (bathes many neurons in low constant amounts of NT instead of discrete packets)

Question 3

What are the two main clusters of the Noradrenergic pathway?

Answer 3

Locus Coeruleus (brain)
Reticular Formation (spine, less important for this course)

Question 4

What areas of the brain are innervated by the Noradrenergic pathway? Which structures specifically?

Answer 4

The whole brain is innervated

Amygdala, hippocampus, and thalamus of note

Question 5

What causes the ‘deer in headlights’ effect during high stress?

Answer 5

Noradrenaline surge in cerebellum causes you to lock up

“You know what this is really important and you need to stop what you’re doing to pay attention”

Question 6

What is a downside to extensive Noradrenergic innervation?

Answer 6

Malfunction in the pathway can cause a host of CNS disorders

Question 7

True/False? The neuroanatomy of the serotonergic pathway is different but the innervation is quite similar

Answer 7

True

Question 8

What is the main cluster of Serotonergic pathways in the brain?

Answer 8

The Raphe nuclei

Question 9

What NT is involved with mood?

Answer 9

5-HT

Question 10

Describe monoamine transmission

Answer 10

DAT, NET, and SERT are localized to perisynaptic sites, to restock vesicles after degradation (drugs inhibit these, causing NT to spend more time in the synapse)

Question 11

What channels transport serotonin? Which has a higher affinity for 5-HT? What is an effect of this?

Answer 11

SERT and PMAT
SERT has a higher affinity but a lower capacity, if it gets clogged PMAT takes over

Depending on which channel you block you can achieve different effects

Question 12

How is serotonin transported in humans?

Answer 12

NA binds to the channel first
Serotonin binds next
Then chloride binds

A conformational change closes the outer pore and opens the inner pore (where the 3 molecules above leave into the cell)

Question 13

What are two possible causes for depression, from a purely synaptic standpoint?

Answer 13

Hypofunction of NA
OR
A hyperfunction of catecholamine transporters

Question 14

Describe the action of a varicosity for an eg NA neuron

Answer 14

AP arrives at varicosity
Depolarization opens CaVs
Ca influx causes exocytosis of synaptic vesicles
NE ginds adrenergic receptor on target
Activity ceases when NE diffuses away from synapse
NE is transported back into the axon
NE can be taken back into synaptic vesicles for re-release or be metabolized by Monoamine oxidase (MAO)

Question 15

Describe the G protein cycle for the Beta 2 adrenergic complex

Answer 15

Receptor presented on cell membrane, alpha beta and gamma subunits linked but not contacting

When agonist binds receptor, it associates with the alpha subunit causing a conformational change which pops GDP out of the alpha subunit
A GTP pops into it causing alpha and beta-gamma subunits to dissociate:
alpha subunit regulates adenylyl cyclase to create cAMP from ATP
beta-gamma subunits open a CaV to increase Ca

Then the alpha GTP gets hydrolized and it all heterotrimerizes again

Question 16

How many serotonin receptors are there? Which is the only one which does not have pharmacology similar to the others?

Answer 16

All the 7 types of serotonin receptor except 5-HT3 have very similar pharmacology