L 9 Synapses And Neurotransmitters - Pt 2

Question 1

What are the criteria for neurotransmitters?

Answer 1

1. Should be present in presynaptic terminal.
2. Should be released in response to stimulation.
3. Should act on the postsynaptic neuron.

Blocking neurotransmitter should prevent synaptic transmission

Question 2

What does immunostaining do?

Answer 2

It helps visualise specific proteins within cells or tissues.
- Fluorescent dyes
- Enzymes that produce a colored product

Question 3

What are the 3 types of neurotransmitters?

Answer 3

Amino acids
Amines
Peptides

Question 4

What can neurons release?

Answer 4

Neurons usually release one kind of neurotransmitter, but some can release more than one.

Peptide-releasing neurons are an example as they can also release a small molecule transmitter, called a ‘co-transmitter’

Question 5

How big are the 3 types of neurotransmitters?

Answer 5

Amino acid and amines are 100 - 200 Da
Peptides are large molecules with 1000 - 3000 Da.

Question 6

Where are the 3 types of neurotransmitters stored in?

Answer 6

Amino acids and amines are stored in synaptic vesicles.

Peptides are stored in secretory granules.

Question 7

Give me 2 types of neurotransmitters receptors

Answer 7

1. Ligand gated ion channels.
2. G Protein coupled receptors.

Question 8

What happens when neurotransmitters binds to a ligand-gated ion channel?

Answer 8

It directly depolarise or hyperpolarise the postsynaptic cell.

Question 9

Can a transmitter (neurotransmitter) activate multiple receptors?

Answer 9

Each transmitter can activate multiple different receptors (divergence)

ACh can activate muscarinic (M1-M5) and nicotonic receptors

Question 10

What type of receptors can the 3 types of neurotransmitters bind to?

Answer 10

Amino acid and amines can bind to ligand-gated ion channels or g-ptotein coupled receptors.

Peptides can bind only to G-protein coupled receptors.

Question 11

Explain what divergence is

Answer 11

Divergence is when a single neurons can amplify its influence and distribute its signal to a larger population of neurons

Question 12

What is the most common excitatory transmitter in CNS?

Answer 12

Glutamate

Gluatemate is responsible for over 90% of the excitatory synaptic connections in the brain

Question 13

How are the 3 ionotropic gluatemate receptors classified?

Answer 13

They are classified based upon their selective agonists, which are synthetic or naturally occuring molecules that preferentially bind to and activate each receptor type

Question 14

What are the 3 glutamate receptors called?

Answer 14

1. AMPA receptors
2. NMDA receptors
3. Kainate receptor

These are all ionotropic

Question 15

How is the action of glutamate terminated?

Answer 15

Terminated by selective uptake into presynaptic terminals and glia.

Question 16

Do AMPA receptors mediate fast or slow excitatory transmission?

Answer 16

They mediate fast excitatory transmission.

Question 17

What are the effects of glutamate binding to AMPA receptors?

Answer 17

Triggers Na+ and K+ currents resulting in an EPSP.

Question 18

Which 2 ionotropic glutamate receptors often co- exist with each other?

Answer 18

NMDA receptors often co-exist with AMPA receptors

Question 19

Which glutamate receptor have a voltage- dependent Mg2+ block?

Answer 19

NMDA receptors

This means when neuron is depolarised, Mg2+ block moves out of the way, thereby unblocking the channel

Question 20

When do NMDA receptors open?

Answer 20

When neuron is already depolarised.

Question 21

What are the effects after NMDA receptors let Ca2+ and Na+ in?

Answer 21

Leads to downstream signalling.

Question 22

What are mGluRs?

Answer 22

Metabotropic glutamate receptors, they allow glutamate to sometimes be inhibitory.

Question 23

What kind of receptors are metabotropic receptors?

Answer 23

They are G-protein coupled receptors.

Question 24

Give me example receptors of mGluRs

Answer 24

mGluR1, mGluR2

Question 25

Describe the mechanism of ionotropic and metabotropic receptors

Answer 25

Ionotropic receptors - Opens ion channels. Metabotropic receptors - Activates G-protein, trigger downstream signalling cascade.

Question 26

Which receptor produces a faster response, ionotropic or metabotropic?

Answer 26

Ionotropic responds in msecs. ## Footnote Metabotropic - seconds to minutes.

Question 27

Do mGluRs allow inhibitory response to glutamate?

Answer 27

Yes sometimes, eg: retina.

Question 28

What is the most common inhibitory transmitter in the CNS?

Answer 28

GABA

Question 29

How is GABA an inhibitory transmitter? What does it do?

Answer 29

GABA produces IPSPs (inhibitory postsynaptic potentials) via GABA-gated chloride channels (GABAA receptors), if the membrane potential is above chloride’s Nernst potential

Question 30

Why is the right amount of inhibition via GABA important?

Answer 30

The right amount of inhibition via GABA is critical: - Too right = coma or loss of consciousness - Too little = seizures

Question 31

What are the other 4 chemicals that can bind to GABA receptors?

Answer 31

1. Ethanol 2. Benzodiazepine 3. Barbiturate 4. Neurosteroids ## Footnote GABA is obviously on as well

Question 32

What are benzodiazepines used for?

Answer 32

They are used to treat anxiety. eg. diazepam.

Question 33

What are Barbiturates?

Answer 33

They are sedatives and anti-convulsants (anti-seizure medications)

Question 34

What are the effects of GABA binding to GPCRs?

Answer 34

GABA binding to GPCRs triggers a cascade of intracellular events: - Open K+ channels - Close Ca2+ channels - Trigger other second messengers like cAMP

Question 35

What is GPCR?

Answer 35

G protein-coupled receptors

Question 36

How do GPCR receptors work?

Answer 36

- When a signaling molecule (like a hormone or neurotransmitter) binds to a GPCR, it causes a conformational change in the receptor - This change activates a G protein, which is loctaed on the inside of the cell membrane - This activated G protein then triggers a cascade of intracellular signaling events, leading to a cellular response

Question 37

What are mGluRs and GABA receptors like?

Answer 37

They're like GPCRs

Question 38

What does glycine do?

Answer 38

Glycine inhibits neurons through glycine-gated chloride channel. ## Footnote Also binds to NMDA gluatemate receptors

Question 39

What is temporal summation?

Answer 39

It's when a single presynaptic neuron fires action potentials in rapid succession.

Question 40

What is spatial summation?

Answer 40

It's when multiple presynaptic neurons release neurotransmitters simultaneously onto different locations

Question 41

Does it matter how excitatory and inhibitory synapses are arranged spatially?

Answer 41

Yes it matters

Question 42

Can an inhibitory synapse block the propagation of an EPSP toward the soma?

Answer 42

An inhibitory synapse can block the propagation of an EPSP toward the soma

Question 43

Do GABA receptors always produce an IPSP ?

Answer 43

No they dont always produce an IPSP.

Question 44

What is shunting inhibition?

Answer 44

Shunting inhibition is when GABAA receptors don’t always produce an IPSP, e.g. if Vm is near chloride’s Nernst potential

Question 45

What are the effects of chloride conductance?

Answer 45

Opening chloride conductance decreases the membrane resistance -> current leaks out the membrane

Question 46

Where does inhibition often occur?

Answer 46

It often occurs presynaptically.

Question 47

Explain the process of presynaptic inhibition

Answer 47

1) Action potential arrives 2) Less calcium enters due to the GABA release which inactivated calcium channels 3) Less Ca2+ = less neurotransmitter released 4) Reduced effect on postsynaptic membrane

Question 48

If AMPA receptors are permeable to both Na+ and K+, why does activating them cause depolarisation?

Answer 48

Glutamate binding to AMPA receptors triggers Na+ and K+ currents resulting in an EPSP

Question 49

What are EPSPs?

Answer 49

Excitatory Postsynaptic potentials

Question 50

What would happen if GABA opens a GABAA receptor and the membrane potential is below chloride’s Nernst potential? Would you get net inflow or outflow of chloride ions?

Answer 50

GABA receptor opens the chloride channel, the electrical force pushing chloride out of the cell will be stronger than the chemical force pulling chloride into the cell. As a result, there would be a net outflow of chloride ions from the neuron (Concentration of Cl- typically higher outside of neuron and inside cell is typically negative (-70mV))

Question 51

What does it mean if membrane potential is above chlorides Nernst potential regarding to GABA receptors?

Answer 51

This means the net movement of chloride ions moves into the neuron due to the force of the chemical gradient (higher extra cellular concentration) being stronger than the electrical gradient acting on chloride