5 - Synapse Structure

Question 1

What is a synapse?

Answer 1

A specialized functional contact zone for communication between nerve cells or between a nerve cell and its effector organ.

Question 2

What is the current flow like at electrical synapses? What type of junction is this?

Answer 2

Bridged/gap junction .

The current flow can be bidirectional or unidirectional.

Question 3

What is the current flow like at chemical synapses? What type of junction is this?

Answer 3

Unbridged junction (presence of a synaptic cleft)

Current flow is always unidirectional from pre-synaptic to post-synaptic cells.

Question 4

Describe the structure of gap junctions in electrical transmission?

Answer 4

Gap onl 3.5 nm wide.

Apposing cells contribute a hemi-channel = connexon

Question 5

How many connexons form an ion channel in gap junctions (electrical transmission)? How do they open?

Answer 5

2 connexons, each made of 6 connexins that each have 4 membrane-spanning regions.

Open via a conformational change in the pore.

Question 6

What is the most rapid form of synapse between neurons with virtually no synaptic delay? Describe the pathway current takes.

Answer 6

Gap junctions with electrical synapses.

They are low resistance, high conductance channels that bridge two cells.

Current flows through the junction and depolarizes the pot-synaptic cell.

Question 7

What are some properties of electrical synapses? What are some down-sides?

Answer 7

Very fast.
Synchronization of transmission between 2 or more electrically coupled neurons.
All-or-none.

No mechanism for inhibitory actions or long-lasting changes in effectiveness (modulation) of synapses.

Question 8

Where are electrical synapses typically found?

Answer 8

In invertebrates.

Also present in the retina and inner ear. More prevalent during development.

Question 9

What is the most common type of transmission in the CNS and PNS? What neurotransmitter is found at the neuromuscular junction? What effect does this have on skeletal muscle vs cardiac muscle?

Answer 9

Chemical transmission.

Acetylcholine: slows contractions of cardiac muscle and conversely causes contractions in skeletal muscle.

Question 10

How is it possible that Ach can have two different effects on cardiac and skeletal muscle?

Answer 10

They have two different types of receptors: muscarinic receptors in cardiac muscle and nicotinic receptors in skeletal muscle.

Question 11

What is chemical transmission mediated by?

Answer 11

Release and diffusion of nts into the synaptic cleft.

Question 12

What are the components of the presynaptic (prejunctional) region of the neuron?

Answer 12

Synaptic vesicles, active zones with presynaptic dense projections that contain Ca dependent calmodulin, and autoreceptors where nts bind to be released.

Question 13

What is located at the postsynaptic region (end-plate; postjunctional)?

Answer 13

Receptors for neurotransmitters, postsynaptic density(PSD), and actin molecules.

Question 14

What is the difference between Gray’s type I and Gray’s type II CNS chemical synapses?

Answer 14

I: Asymmetric with round synaptic vesicles, wide synaptic cleft, prominent post synaptic densities, and is often associated with excitatory synapses (
cholinergic or glutamatergic).

II: Symmetric with flat or pleomorphic vesicles, a narrow cleft, less prominent Postsynaptic densities, and often associated with inhibitory synapses (gaba or glycine)

Question 15

What are characteristics of monoaminergic synapses?

Answer 15

Dense-core vesicles, axonal varicosities, wide synaptic cleft, and no prominent pre- and postsynaptic densities.

Norepi, epi, serotonin, and 5HT.

Question 16

What do peptidergic synapses contain?

Answer 16

Large dense-core vesicles that are often of different sizes and shapes.

Question 17

What is the structure of neuromuscular junctions? What is located there?

Answer 17

Presynaptic dense bars, Ca++ channels, primary and secondary synaptic clefts, AchE and basal lamina clefts, postsynaptic junctional folds, Ach receptors, and voltage gated Na channels along sides and depths of folds.

Question 18

What is located within the synaptic cleft itself?

Answer 18

Enzymes that degrade Ach called acetylcholine esterases.

Basal lamina also there, which is important for regeneration.

Question 19

What is Myasthenia Gravis (MG)? What are symptoms and causes?

Answer 19

Disease of chemical transmission at the neuro-muscular junction causing severe weakness of muscles.

Most common cause is autoimmunity: antibodies against one’s own nicotinic ach receptors in muscles.

Congenital and heritable is rqare.

Question 20

What is the treatment for myasthenia gravis (MG)?

Answer 20

Inhibitors of acetycholinesterases.

Question 21

What is Lambert-Eaton Myasthenic Syndrome (LEMS)?

Answer 21

Antibodies against one’s own presynaptic voltage-gated calcium channels.

Question 22

What are the steps involved in a synaptic vesicle releasing its contents in the synaptic cleft?

Answer 22

1. Approach
2. Attach
3. Contact the PM
4. Fusion
5. Fission - opens so nts released
6. Collapse - of vesicles
7. Retrieval - for recycling
8. Recycling

Question 23

Where is the tetanus toxin found and what are its effects?

Answer 23

Soil and rusty wires.

It cleaves VAMP and doesn’t allow the release of GABA, resulting in reduced inhibition.

Excitatory nts take over, leading to generalized muscle spasms (spastic paralysis).

Question 24

Where is botulinum toxin found and what effect does it have?

Answer 24

In improperly processes meats.

Cleaves VAMP (v-snare) or t-snare and prevents the release of nts so muscles become weak and flaccid paralysis occurs.

Question 25

Where is alpha-Latrotoxin found and what effect does it have?

Answer 25

Found in black widow spiders.

It binds to neurexin and causes release of nts from synaptic vesicles and can cause spasms and sometimes death.

Question 26

What is the function of synapsin I?

Answer 26

Binds vesicles to cytoskeleton; phosphorylated by Ca/calmodulin dependent protein kinase when intracellular Ca is increased to cause release of vesicles from the cytoplasm.

Question 27

What is Rab3A?

Answer 27

Neuron-specific GTPase that binds to vesicles and is essential for propelling vesicles to the active zone.

Question 28

What is the major Ca++ sensing protein that triggers vesicular exocytosis?

Answer 28

Synaptotagmin

Question 29

What is NSF? What binds to it?

Answer 29

Cytosolic ATPase that hydrolyzes ATP to release the complex.

SNAP binds to it.

Question 30

What are v-SNARE and t-SNARE? What are the components of each?

Answer 30

v-snare (aka VAMP) - has synaptobrevin on vesicular side and binds t-snare.

t-snare is located in the PM of the presynaptic site. Two components: syntaxin and SNAP-25.

Both involved in docking and fusion.

Question 31

What are neurexin and neuroligin?

Answer 31

Neurexin: PM protein that interact with vesicle proteins.

Neurologin: post-synaptic PM protein that interacts with neurexin across the cleft (two shaking hands).

Question 32

After the AP is propelled down the axon terminal, how are the vesicles prepared for docking at the active zone?

Answer 32

Dephosphorylated synapsin I anchors the vesicles to the cytoskeletal proteins.

Once phosphorylated, synapsin I releases the vesicles from the network and Rab3A helps propel them toward the active zone.

Question 33

What happens after Rab3A propels the vesicles towards the active zone?

Answer 33

V and T snare interact and vesicle fuses with the PM; this is triggered by Ca binding to synaptotagmin on the vesicle membrane.

Nts are released from presynaptic neuron via exocytosis.

Question 34

What are the characteristics of direct gating in receptor-gated chemical transmission? What is the structure?

Answer 34

Fast time domain.

The receptor is part of the ion channel - called ionotrophic.

Many have 5 subunits, each containing 4 transmembrane domains.

Question 35

What are the characteristics of indirect gating in receptor-gated chemical transmission? What is the structure?

Answer 35

Slow time domain.

Receptor actives G-protein - called metabotrophic receptors.

Second messenger (cAMP or cGMP) cascade.

Typically have 1 subunit with 7 transmembrane domains.

Question 36

What are properties of chemical transmission?

Answer 36

Amplification of synaptic responses, plasticity of synaptic responses, diversity of synaptic types and transmitters, neuromodulation, and synaptic delay.

Question 37

What is gaseous transmission mediated by? What is their structure? What are two exampls of gaseous messengers?

Answer 37

Mediated by synthesis and diffusion of gaseous messenger (neurotransmitter) from presynaptic to postsynaptic cell.

No unique ultrastructual specializations.

Exp: NO and CO.

Question 38

What is the function of nitric oxide? carbon monoxide?

Answer 38

NO: Increases production of cGMP.
-Vasodilation of blood vessels, antimicrobial in immune system, relaxation of smooth muscle in GI, associated with learning and memory in the brain.

CO: deadly, but small amounts can act as nts to increase cGMP production.

Question 39

What are the steps that occur in a neuro-neuronal synapse (gaseous transmission)?

Answer 39

1. Glutamate released from pre terminal and binds to NMDA receptors.
2. Ca++ enters through receptors and activates NOS
3. nNOS (neuronal NO synthase) produces NO while converting arginine to citruline
4. NO acts in postsynaptic cell or diffuses to neighboring neurons.

Question 40

What happens in the neuro-effector synapse of smooth muscle cells?

Answer 40

Ca++ entry activates nNOS to make NO.

NO diffuses into smooth muscles or effector organs to act and cause relaxation.

Question 41

Where does NO binds in the postsynaptic cell? What does this cause?

Answer 41

To ion in a heme moiety attached to guanylate cyclase to activate it and produce cGMP.

cGMP activates cGMP dependent protein kinase which alters the gating of ion channels in the membrane.

Question 42

What is the direction of gaseous synapses?

Answer 42

Unidirectional.