Chapter 5: Synaptic Transmission

Question 1

Overall Process

What is the overall process of synaptic transmission?

Answer 1

1. Nuerotransmitter releases across synaptic cleft
2. Bind to receptors on the post -synaptic side on the dendrites & soma
3. When it binds, a ligand- gated ion channel will either open or close
4. EPSPs and IPSPs constantly go into the cell or neuron and then it will be summed to see if we can initiate an action potential once again!

Chemical —> Electrical —-> Chemical

Question 2

A Brief History

Compare and describe the differences between the reticular theory and the neuron doctrine in the sense of electrical and chemical transmission…

Answer 2

**Reticular Theory (Golgi)
*** Flow of signals was purely electrical and there was a continuos flow

Neuron Doctrine (Cajal)
* ****Current would flow out into the extracellular spce
* A chemical signal (neurotransmitter) is relseased by the cell sending the signal to the (presynaptic cell)
* Does something to the cell recieveing the signal.

Both were right :)

Question 3

A Brief History

What are synapses and does it have to be between two neurons?

Answer 3

Synapses is the functional connection between two cells and it can be between 2 neurons or even between a neuron and a muscle cell.

Question 4

A Brief History

In what way does the information flow?

Answer 4

Unidirectional. It goes from pre synaptic to post synaptic.

There are exceptions to this but for now this is okay.

Question 5

A Brief History

Describe the Loewi Experiement

Answer 5

Gave us the first evidence of pure synaptic chemical transmission.
* He put two frogs hearts into seperate solutions but the first still had the vagus nerve attached. He used a tube to connect both solutions with the hearts in it.
* The heart rate of heart one slowed and then as the solution was transferred to heart 2, the heart rate also slowed.

Question 6

Electrical Synapses

Describe electrical synapses

Answer 6

• Electrical synapses allows direct transfer of ionic current from one cell to the next.
• Occurs at the neuronal gap junctions which are found in several brain regions.
• There are connexons on both pre-synapctic and post-synapctic sides and they bring the cells very close in contact.

Question 7

Electrical Synapses

What are gap junctions channels made up of?

Answer 7

• Formed by 2 connexons
• A connexon is formed by 6 connexins

Question 8

Electrical Synapses

What exactly do gap junctions do?

Answer 8

* They allow the flow of ions from cytoplasm of one cell to cytoplasm of another cell
* Allows bi-directional flow of ionic current
* Very Fast transmission
Ex. flies are really fast b/c of this.

Question 9

Chemical Synapses

Describe the pre-synaptic & post-synaptic sides

Answer 9

Presynaptic Side
* Axon terminal
* Neurotransmitter vesicles & secretory glands
* Active zones: sites of neurotransmitter release

**Postsynaptic Side
* **Post Synaptic Denstiy: Contains Neurotransmitter receptors

Question 10

Chemical Synapses

How wide is a synaptic cleft?

Answer 10

20-50 nm wide

Question 11

Chemical Synapses

Compare electrical vs. chemical synapses

Answer 11

Electrical
* Gap junctions connect cytoplasm of pre & postsynaptic cell
* Bidirectional
*** Ionic current flows through gap junctions channnels that bridge pre and post synaptic cells **
* If post synaptic cells is depolarized then it causes an action potential

Chemical
* Neurons seperated by synaptic cleft
* No current crosses from pre to post
* **Action Potential leads to release of chemical transmitter that diffuses across synaptic cleft **
* Transmitter interacts with receptors on postsynaptic cell»_space;> depolarization or hyperpolarization.

Question 12

Chemical Synapses

You are recording from a pre-and post synaptic neuron. You measure a post-synaptic potential (PSP) in the presynaptic neuron and almost instantly see an PSP in the post-synaptic neuron . This is an example of a chemical synapse.

T/F

Answer 12

False
Has to be an electrical synapse because a chemical synapse isn’t that fast.

Question 13

Properties of Chemical Synapses

What are the types of CNS synapses?

Answer 13

• Axodendritic: Axon to dendrite
• Axospinous: Axon to dentritic spine
• Axosomatic: Axon to axon
• Axoaxonic: Axon to Axon <— can cause more or less neurotransmitters to be released b/c nerve terminals of neurons are touching each other.

Question 14

Properties of Chemical Synapses

What are autoreceptors and what are their purpose?

Answer 14

Autoreceptors are presynaptic receptors sensitive to neurotransmitter released by the presynaptic terminal.
* **located outside active zone and far from post synaptic density so if a neurotransmitter gets close to it then there is too many being released. **
* When too many neurotransmitters are released, they inhibit it and functions as a safety valve (negative feedback) by informing neuroterminal to stop releasing neurotransmitters.

Two different types:
* Terminal (located on the nerve terminal)
* Somatodendritic (located on soma or dendrites)

Question 15

Properties of Chemical Synapses

Compare and contrast Gray’s type 1 to Gray’s type 2

Answer 15

Gray’s type 1: Asymmetrical ; usually excitatory
Gray’s type 2: Symmetrical; usually inhibitory

Question 16

Properties of Chemical Synapses

What are archetypal synapse: Nueromuscular Junctions (NMJ)

Answer 16

• Chemical synapses exist between motor neurons of the spinal cord and skeletal muscle - the NMJ
• Established the principles of synaptic transmission
• One of the largest synapses in the body
• Not all synaptic junctions exists in the CNS**

Question 17

The Process of Chemical Synaptic Transmission

Give a brief overview of Chemical Synaptic Transmission

Answer 17

• Neurotransmitter/peptide synthesis
• Packaging into synaptic vesicles
• Vesicles fusions
• Neurotransmitter release into synaptic cleft
• Binding to post synaptic receptors
• Biochemical/electrical response elicited in postsynaptic cell
• Removal of neurotransmiter from synaptic cleft

Question 18

Neurotransmitters

What is the classical criteria to determine whether a chemical is a neurotransmitter?

Answer 18

1. The substance must be present in the presynaptic terminal
2. The substance must be released in response to presynaptic depolarization and the release must be calcium-dependent.
3. Specific receptors for the substance must be present on the postsynaptic cell.

Question 19

Neurotransmitters: Synthesis & Storage

What must neurotransmitters be in order to be ready for release?

Answer 19

Synthesized and readied.
* Nuerons have many neurotransmitters that are abundant.
* Each neuron contains specialized enzymes required to synthesize the NT in the nerve terminal.

Question 20

Neurotransmitters: Synthesis & Storage

What are vesicular transporters?

Answer 20

**They are in the vesicular membrane and concentrate NTs into synaptic vesicles **
* Small, clear-core vesicles
* Packing into synapctic vesicles protects NT from breakdown by enzymes in presynaptic terminal.

Question 21

Neuropeptides: Synthesis & Storage

What are neuropeptides?

Answer 21

Synthesized in the ER, split in the Golgi, and bud off into a secretory granule.
* Large, dense-core vesicles
* Precursor proteins ar broken down by enzymes during shipment to axon terminals - peptide is “liberated”
* No replenished very quickly

Question 22

Neuropeptides: Synthesis & Storage

Neurotransmitters vs. Neuropeptides

Answer 22

• NP Release: Greater depolarization needed
• Vesicle Size: Small clear vs large dense core vesicles.

Question 23

Neurotransmitters: Release

What is Ca2+ mediated exocytosis and how does it work?

Answer 23

• When a wave of depolarizatio reaches the axon terminal»>voltage -gated Ca2+ channels open.
• Neurotransmitter release is depended on the influx of calcium into pre- synaptic terminal to allow synaptic vesicles or secretory granules to fuse to pre-synaptic membrane and release their contents into the synaptic cleft.
  * Ca2+ sensitive proteins causes the vesicles to fuse with the cell membrane, releasing neurotransmitters

Question 24

Neurotransmitters: Release

What are SNARE Proteins and what do they do?

Answer 24

SNARE Proteins bring two membranes close together.
* Synaptobrevin in synaptic vesicle membrane
* Syntaxin & SNAP -25 in plasma membrane

Question 25

# Neurotransmitters: Release What is the calcium binding protein?

Answer 25

Synaptotagmin which is located in the vesicle membrane and it the **calcium sensor.** * It causes the SNARE proteins to fuse together causing the fusion of the vesicle membrane with the plasma membrane allowing the NTs to be released in the synaptic space.

Question 26

# Neurotransmitters: Release What is botulism?

Answer 26

It is a bacterial toxin that blocks ACh release at neuromuscular junctions * Enzymes in the toxin attack SNARE proteins by cleaving or cutting it. * this is what is used in botox

Question 27

# Neurotransmitters: Release Describe the process of vesicle recycling?

Answer 27

* During exocytosis, vesicle membranes are added to the cell membrane * Vesicle membrane is recycled by endocytosis and then fuses with an endosome *** Clathrin** protein coats vesicles for recycling | Clathrin plays a role in shaping vesicles in the cytoplasm.

Question 28

# Neurotransmitter Receptors: Ionotropic Receptors What are ionotropic receptors? | Also called Transmitter-gated ion channels

Answer 28

* They are ion channels that open in response to neurotransmitter binding to them. * Ions then enter the cell and a **postsynpatic potential (PSP)** is produced, also called "local potentials" because this is happening near the membrane.

Question 29

# Neurotransmitter Receptors: Ionotropic Receptors What are the two kinds of PSPs produced?

Answer 29

**Excitatory Postsynaptic Potential (EPSP) *** A positive charged ion enter the cell and causes depolarization of the membrane which makes it more likely to fire an action potential. Ex. glutamate **Inhibitory Postsynaptic Potential (IPSP)** * A negative charged ion enters the cell and causes hyperpolarization which decreses the chances to fire an AP. Ex. GABA

Question 30

# Neurotransmitter Receptors: Ionotropic Receptors Can there be more than one input on a single neuron?

Answer 30

Yes! There can be thousands of inputs on a single neuron and then these inputs are summed and if the sum reached the threshold then an AP results * None of the PSPs are sufficient to depolarize the cell by themselves.

Question 31

# Neurotransmitter Receptors: Ionotropic Receptors Describe EPSPs detailed

Answer 31

* Na+ inward current flow causes the membrane depolarization, more likely to fire AP.

Question 32

# Neurotransmitter Receptors: Ionotropic Receptors Describe IPSPs Detailed

Answer 32

Cl- inward current flow causes the membrane hyperpolarization; less likely to fire an action potential.

Question 33

# Neurotransmitter Receptors: G- Protein Coupled Receptors (GPCRs) What are the two types of receptors

Answer 33

G-protein Coupled Receptors & Ionotropic Receptors

Question 34

# Neurotransmitter Receptors: G- Protein Coupled Receptors (GPCRs) What are G-protein coupled receptors? | Also known as metabotropic receptors

Answer 34

They are inserted in the plasma membrane and when NTs bind to them, they act in two ways: 1. They can directly inhibit or activate and ion channel located near it. 2.** They can stimulate or inhibit effector enzymes in the cell membrane that synthesizes or break down second messenger moleucles. **

Question 35

# Neurotransmitter Receptors: G- Protein Coupled Receptors (GPCRs) Describe more about these second messengers

Answer 35

* **The first messengers are the NTs. * ***They will bind to the first receptors. **The second messengers are molecules inside the cell produced by effector enzymes that activate protein kinases. ** * Causes phosphorylation of substrate proteins * Ex. (cAMP)

Question 36

# Neurotransmitter: Degradation & Recovery how does neurotransmitters stop signal transmission?

Answer 36

They must be REMOVED from the synaptic cleft ;0 1. **Diffusion** of transmitter molecules away from the synapse. 2. **Reuptake via transporters**: Neurotransmitter re-enters presynaptic axon terminal or that of neighboring astrocyte. 3. **Enzymatic Destruction**: inside nerve terminal or in the synaptic cleft. Ex. AChE

Question 37

# Neurotransmitter: Degradation & Recovery What are some of the transporters that blocks the re-uptake of Serotonin?

Answer 37

* SSRIs * MDMA * Cocaine

Question 38

# Neurotransmitter: Degradation & Recovery What are agonists & antagonists

Answer 38

**Agonists**: mimic the actions of naturally occuring neurtotransmitters **Antagonists**: Inhibitors of neurotransmitter receptors

Question 39

# Taking it all in What is synpatic integration?

Answer 39

Synaptic integration is the process by which multiple synpatic potentials combine within one postsynaptic neuron. * Most CNS neurons recieve thousands of synaptic inputs.

Question 40

# Taking it all in What is EPSP summation and what are the two type?

Answer 40

Integration: EPSPs added together to produce significant postsynaptic depolarization. * **Spatial summation**: EPSPs generated simultaneously at different sites * **Temporal summation:** EPSPs generated at same synapse in rapid succession.

Question 41

# Taking it all in Describe Dendritic Cable Properties

Answer 41

* Signal is not regenerated in dendrites (spreads passively) * Membrane depolarization falls off exponentially with increasing distance along the cable * Dendrite can be viewed as a straight cable

Question 42

# Taking it all in Describe Inhibition

Answer 42

* Not all synapses are excitatory * Action of inhibitory synapses:** take membrane potential away from action potential threshold. ** * Exerts powerful control over neuron output.

Question 43

# Taking it all in Describe Shunting Inhibition

Answer 43

This is when a synapse inhibits current flow to the axon hillock. * The depolarizing current is inhibited by inhibitory synpases such as GABA or glycine. * Knocks down effect of excitatory ion and prevents AP from happening. * Located on soma and near axon hillock

Question 44

# Taking it all in Describe Modulation

Answer 44

Many synpases have GPCRs that are not directly associated with an ion channel. * Therefore activiation of these receptors do not produce EPSPs or IPSPs. * Instead, it modifies the efficacy of EPSPs generated by other synapses which allows the effects to last longer than the prescence of NT on receptor.