Lecture 3B: Neurotransmitters And Neuromodulators

Front 1

What are the majority of synapses?

Back 1

The majority of synapses are axodendritic (axons connecting with dendrites)

Front 2

What other type of synapse besides axodendritic synapses are there a lot of?

Back 2

axosomatic synapses

Front 3

What are the other types of synapses besides axodendritic & axosomatic synapses?

Back 3

dendrodendritic and axoaxonic synapses: dendrodendritic synapses are synapses where the dendrites touch that are common in interneurons & axoaxonic synapses are axons touching axons and are involved in presynaptic inhibition of neurotransmission

Front 4

What is a neurotransmitter?

Back 4

A chemical, gas, or hormone that is synthesized in and released from a neuron.

Front 5

where are large neurotransmitters synthesized/held?

Back 5

Large neurotransmitters are synthesized in the cell body and are then transported down the axon to the terminal

Front 6

where are small neurotransmitters synthesized/held? (what are they held in?)

Back 6

Small neurotransmitters are synthesized in the terminals and are stored there in vesicles

Front 7

when does release of a neurotransmitter occur?

Back 7

release of a neurotransmitter occurs when vesicles dump neurotransmitters into the synaptic cleft

Front 8

what are the steps of neurotransmission?

Back 8

1. axon potential travels down the axon of the presynaptic neuron
2. the depolarization of the membrane in the terminals causes voltage-gated calcium (Ca+2) channels to open--> Ca2+ enters
3. Ca2+ turns on machinery to move the vesicles to the "active zone"
4. The membrane of the vesicles fuses the cell membrane in the "active zone" and neurotransmitters are released into the synaptic cleft.
5. The neurotransmitters interact with receptors on the postsynaptic neuron causing PSPs

Front 9

Describe small molecule exocytosis & when does it occur?

Back 9

Small molecules are released in pulses when the calcium signal is sent.

Front 10

describe large-neurotransmitter exocytosis & when it occurs.

Back 10

large neurotransmitters are only released when there are higher rate of neuron firing (action potentials) and calcium levels rise in the terminal button.

Front 11

does the neuron have only one type of neurotransmitter that it produces?

Back 11

No, in many neurons, there are both a small molecule neurotransmitter and a large molecule neurotransmitter.

Front 12

what are the three ways that neurotransmission is ended & describe each of them. which one is not very common?

Back 12

1. Diffusion: neurotransmitters simply move out of the synaptic cleft (problem- takes a very long time too long)
2. Reuptake: transporters in the terminals (or on the dendrites) take the neurotransmitter back inside the neuron to be re-packaged or degraded
3. Enzymatic degradation: enzymes found in the synaptic cleft break down the neurotransmitter after it is released (not very common)
(sometimes you have a combination… such as a reuptake into the terminal and then after that enzymatic degradation)
(the idea is to get rid of the neurotransmitter before it binds to the receptor again)

Front 13

what are autoreceptors? (where are they located and what do they do?)

Back 13

Autoreceptors: receptors located on the edges of the active zone of the presynaptic terminal; regulate calcium channels and the machinery involved in exocytosis

Front 14

what is negative feedback?

Back 14

receptors are the same as the thing they release so that they will stop firing (neuron regulates itself!) called NEGATIVE FEEDBACK

Front 15

what happens if a cell is very active & what happens as a result of that?

Back 15

if a cell is very active, firing a lot, then a lot of neurotransmitter accumulates in the axon terminal and as a result the cell will stop producing new neurotransmitters

Front 16

what happens if regulation of neurotransmission fails?

Back 16

if regulation broken down: serious problems

Front 17

what are the four classes of small-molecule neurotransmitters?

Back 17

amino acids, monoamines, soluble-gas neurotransmitters, and acetylcholine (Ach)

Front 18

what are monoamines?

Back 18

all made from one amino acid that by some enzymatic reaction was changed; more diffuse effects than amino acid neurotransmitters (varicocisities)

Front 19

what are amino acids?

Back 19

1. building blocks of proteins) most common neurotransmitters in the nervous system
-mediates the majority of fast-acting, directed synapses
-uses reuptake mechanisms

Front 20

what are the excitatory amino acids (small-molecule neurotransmitters)?

Back 20

the excitatory amino acids are glutamate and aspartate.

Front 21

what are the inhibitory amino acids (small-molecule neurotransmitters)?

Back 21

-GABA- made from glutamate in neurons and astrocytes
-Glycine

Front 22

what is GABA made from?

Back 22

GABA is made from glutamate in neurons & astrocytes

Front 23

what are the monoamines?

Back 23

Dopamine, epinephrine (adrenalin), norepinephrine, and serotronin

Front 24

how are the monoamines divided?

Back 24

1. catecholamines-made from tyrosine- dopamine, epinephrine, and norepinephrine
2. indolamines- made from tryptophan- serotonin

Front 25

where are enzymes found that convert tyrosine and tryptophan?

Back 25

enzymes that convert tyrosine and tryptophan are found in both the cell bodies & terminals

Front 26

how do monoamines end their activity?

Back 26

monoamines use reuptake to end their activity.

Front 27

what happens to some of the tyrosine in your blood stream?

Back 27

tyrosine
Ldopa
dopamine
norepinephrine
epinephrine

Front 28

what is dopamine?

Back 28

-Dopamine is a monoamine made from tyrosin and therefore called a catecholamine.
-secreted when we take any drug of abuse
-in some ways, strongly involved in reward, reinforcement, learning & motivation
-important in motor control

Front 29

what is serotonin?

Back 29

made from tryptophan (indolamine), so if you do not have enough tryptophan, you have a mood disorder
-involved in mood regulation, dreaming, learning, aggression, etc.
-(LSD works on serotonin mostly)

Front 30

what are soluble gas neurotransmitters?

Back 30

-small molecule neurotransmitters (nitric oxide & carbon monoxide)
-made in the cell body & diffuse across the membrane to all directions—not secreted through the terminals (due to smallness- have this ability)
-probably play a role in retrograde signaling (from postsynaptic neuron to presynaptic neuron)-regulation mechanism
- THC
-very short-lived… broken down inside cells quickly by enzymes

Front 31

what are the soluble gas neurotransmitters?

Back 31

nitric oxide and carbon monoxide

Front 32

where are neurotransmitters made/ released?

Back 32

made in the cell body & diffuse across the membrane to all directions (due to smallness- have this ability)—not secreted through the terminals

Front 33

what do soluble-gas neurotransmitters play a role in?

Back 33

probably play a role in retrograde signaling (from postsynaptic neuron to presynaptic neuron)-regulation mechanism

Front 34

how are soluble-gas neurotransmitters removed?

Back 34

very short-lived… broken down inside cells quickly by enzymes

Front 35

What is Acetylcholine (Ach)?

Back 35

made from putting an acetyl group onto choline

Front 36

How is Acetylcholine gotten rid of?

Back 36

degraded in the synapse by acetylcholinesterase (AchE) (chops the acetyl group off the choline) & then reuptake

Front 37

What does Acetylcholine do?

Back 37

involved in memory/learning, smoking tobacco works on acetylcholine receptors, extremely important for the activation of muscle contractions

Front 38

What if Acetelcholineterase (AchE) is not there?

Back 38

then the muscles are locked- they stay contracted

Front 39

What does the weapon nerve gas do?

Back 39

it causes paralysis because it gets rid of the Acetylcholinesterase (AchE).

Front 40

what types of large molecule neurotransmitters are there?

Back 40

one type- peptides

Front 41

What are peptides & what does not produce them?

Back 41

-larger molecules that more resemble proteins (terminal does not produce them)
-[over 100 different peptide neurotransmitters in the brain- endorphins (pain & pleasure) are the most famous ones; slower signaling than the small molecule neurotransmitters; broken down by degradative enzymes in the synaptic cleft; their effect is more GRADUAL than that of small molecule neurotransmitters; endorphins used during stress so that we can function & rescue ourselves despite being in serious pain]

Front 42

How many peptides are in the brain?

Back 42

over 100 different peptide neurotransmitters in the brain

Front 43

What are the most famous peptides?

Back 43

endorphins (pain & pleasure) are the most famous ones

Front 44

signaling in small-molecule neurotransmitters vs. large-molecule neurotransmitters (peptides)

Back 44

lpeptides have slower signaling than the small molecule neurotransmitters

Front 45

How/where are peptides gotten rid of?

Back 45

degradation- broken down by degradative enzymes in the synaptic cleft

Front 46

How does the effect of peptides differ from the effect of small-molecule neurotransmitters?

Back 46

The effect of peptides is more GRADUAL than that of small molecule neurotransmitters

Front 47

What are endorphins & when are they used?

Back 47

-most famous large molecule neurotransmitters (peptides)
-pain and pleasure
-endorphins used during stress so that we can function & rescue ourselves despite being in serious pain

Front 48

what are receptors?

Back 48

receptors are specialized proteins that are capable of binding neurotransmitters and signaling to the cell (allow PSP to happen- translation of neurotransmitter into PSP)

Front 49

where are receptors located?

Back 49

-can be located postsynaptically
-receptors can be located presynaptically also (where they feedback onto the “sending” neuron)=autoreceptors

Front 50

what is specific interaction?

Back 50

-receptors have specific sites that neurotransmitters and drugs recognize specific interaction

Front 51

how many receptors are there for each neurotransmitter (and vice versa)?

Back 51

-receptors respond in almost all cases to only one type of neurotransmitter; however, one neurotransmitter can have many types of receptors with different affects

Front 52

what are ionotropic receptors?

Back 52

-ion-attracting receptors
-ion channels and allow either + or – ions (Na-, Ca2+ or – ions (Cl) to cross membrane
-Referred to as ligand-gated ion channels (you can have ligands that are artificial)

Front 53

what types of ligands are there?

Back 53

real and artifical ligands

Front 54

what does sodium cause?

Back 54

sodium causes excitatory postsynaptic potential

Front 55

what are the 2 types of ligands?

Back 55

1. neurotransmitters
2. drugs

Front 56

what is "fast neurotransmission" & by which channels does it happen?

Back 56

-just as voltage-gated ion channels rapidly influence the membrane potential, so do ligand-gated ion channels

Front 57

what is presynaptic inhibition?

Back 57

-occurs by axoaxonal synapses combined with another type of synapse
-happens with EPSPs only
-B inhibits the excitatory effects of A on C by partially depolarizing the button of A, so that action potentials traveling down A produce a smaller change in the membrane potential and thus release less neurotransmitter onto C.

Front 58

when does presynaptic inhibition occur?

Back 58

when there is an absense of inhibitory neurotransmitters or IPSPs

Front 59

what are the 7 processes of neurotransmitter action?

Back 59

1. neurotransmitter molecules are synthesized from precursers under the influence of enzymes
2. neurotransmitter molecules are stored in vesicles.
3. neurotransmitter molecules that leak from their vesicles are destroyed by enzymes.
4. action potentials cause vesicles to fuse with the presynaptic membrane and release their neurotransmitter molecules into the synapse

Front 60

metabotropic receptors

Back 60

-also called G-protein receptors
-when metabotropic receptors are activated, they release a protein complex called a G-protein that breaks apart and its subunits produce various effects inside the cell

Front 61

After the G-protein is broken down into subunits, what do the subunits do?

Back 61

-some subunits activate K+ channels from the insidehyperpolerization IPSP
-some subunits activate Na+ channels or Ca2+ channels from the inside EPSP and neurotransmission
-some subunits activate second messengers (intracellular enzymes involved in transmitting the neurotransmitter signal; e.g., CAMP) and they can, in turn, alter ion channels, receptors, gene transcription, etc.

Front 62

types of metabotropic receptors

Back 62

-metabotropic receptors that are coupled to Gs Proteins stimulate second messenger signaling
-metabotropic receptors that are coupled to Gi proteins inhibit second messenger signaling

Front 63

What do Gi and Gs proteins do and why?

Back 63

They slow down or delay neurotransmission.

Front 64

Do receptors recognize all ligands? What is the interaction of receptors with ligands based on?

Back 64

Receptors only recognize certain ligands and this interaction is based mostly on the chemical structure of the ligand

Front 65

Describe the interaction between a particular receptor and its neurotransmitter.

Back 65

-since neurotransmitters have different chemical structures, the interaction between a particular receptor and its neurotransmitter is specific (unique) *e.g. only glutamate can activate glutamate receptors

Front 66

Is their just one receptor for each neurotransmitter? What is the effect of this?

Back 66

there exist multiple receptors for every neurotransmitter so one neurotransmitter can activate a number of different receptors.

Front 67

True or false: a neurotransmitter binds to either metabotropic or iontropic receptors

Back 67

FALSE!
Some neurotransmitters have both metabotropic and ionotropic receptors (e.g. glutamate, GABA, epinephrine, acetylcholine, serotoninfast & slow transmission

Front 68

Some neurotransmitters can bind to either metabotropic or iontropic receptors. What is the effect of this?

Back 68

fast and slow transmission

Front 69

Which neurotransmitters can bind to both metabotropic receptors and iontropic receptors?

Back 69

glutamate, GABA, epinephrine, acetylcholine, serotonin

Front 70

Can a neurotransmitter activate both Gs and Gi receptors?

Back 70

yes, a neurotransmitter can activate both Gs and Gi receptors

Front 71

True/false: Glutamate is an excitatory neurotransmitter.

Back 71

False.
-glutamate is often considered the “excitatory neurotransmitter” in the brain
-bottom line: it ain’t excitatory--- the postsynaptic receptors it actives are + ion channels (EPSPs) and Gs-coupled metabotropic (EPSPs)

Front 72

Glutamate activates which receptor/s?

Back 72

the postsynaptic receptors it activates are + ion channels (EPSPs) and Gs-coupled metabotropic (EPSPs)

Front 73

Dopamine activates which receptor/s?

Back 73

-only metabotropic receptors

Front 74

Why is dopamine considered a neuromodulator?

Back 74

dopamine is considered a neuromodulator because it activates only metabotropic receptors and thus its signaling is relatively slow

Front 75

Are autoreceptors iontropic or metabotropic? What do they do?

Back 75

-autoreceptors are metabotropic
-may inhibit any of the steps in neurotransmitter synthesis, packaging, docking, & release

Front 76

What type of receptor does dopamine combine to?

Back 76

-metabotropic receptors
-postsynaptic dopamine receptors can be either Gs- or Gi coupled

Front 77

Is dopamine stimulatory or inhibitory?

Back 77

Dopamine can be either stimulatory or inhibitory.