Lecture 20; Synapse Plasticity 2

Question 1

Describe the changes in energy phase during synaptic transmission;

Answer 1

Electrical AP is converted into Chemical Potential then back to electrical AP

Question 2

What is crucial to synaptic function?

Answer 2

The synaptic density proteins must be in the right place at the right time in the pre and post synaptic clefts

Question 3

Describe mature synapses;

Answer 3

High specialised complex structures

Question 4

What are the three main phases of synaptic development?

Answer 4

Phase 1. Contact between axon and dendrite

Phase 2. Induction of synaptic differentiation

Phase 3. Maturation of developing synapses

Question 5

Describe what happens initially when neurons differentiate;

phase one

Answer 5

They extend processes called neurites.

Specific processes occur to determine if neurites become axons or dendrites

Question 6

What determines the route of growth for a neurite?

Phase One

Answer 6

The GROWTH CONE is the leading edge of the axon or dendritwe

•The leading edge of the growth cone, the LAMELLIPODIUM, is a ruffled sheet of membrane from which protrude FILOPODIA

Question 7

What is the function of the growth cone?

Phase One

Answer 7

it is specialised to charter new territory for neurite elongation

Question 8

What role do filopodia have?

Phase One

Answer 8

•Filopodia constantly extend and retract from the lamellipodium, searching the environment until its attachment leads to neurite extension and outgrowth in that direction.

Question 9

What can initiate the formation of the synapse?

Phase One

Answer 9

• Both axons and dendrites extend growth cones, elongate and branch
• Both axons and dendrites have an active role in the initiation of contact and synapse formation

NOT just an axon thing

Question 10

In reality what is more likely to create a synapse? axon or dendrite?

Phase One

Answer 10

Dendrites are more likely;

– numerous synaptic contacts formed during development are located on dynamic dendritic growth cones and filopodia

Question 11

How do dendrite filipodia differ from axonal ones?

Phase One

Answer 11

Dendritic filopodia display highly dynamic protrusive behaviour and induce the formation of presynaptic terminals along axonal shafts

Question 12

What happens at the site of dendritic or axonal contact?

Answer 12

Axonal and dendritic compartments at the contact site differentiate into a presynaptic bouton and a postsynaptic receptive apparatus

Question 13

Describe what is happening when the dendritic and axonal compartments connect?

Answer 13

Bridges form across the synapse to draw receptors in together

Prior to synapse differentiation, receptors wonder aimlessly around the membrane.

Question 14

What sends signals to cluster NMDA receptors?

Answer 14

Ephrin

Question 15

What signals for synapse differentiation?

Answer 15

–Neuroligins –ADHESION MOLECULES (can induce presynapse in epithelia cells)

–Ephrin/ephB receptors–INTERACT ACROSS THE SYNAPSE (1/2) (induce clustering of NMDA receptors)

–Pentraxins (Narp) –SECRETED FROM PRESYNAPSE (cluster AMPA receptors

Question 16

Whats the reality of synapse differentiation molecules?

Answer 16

Induction likely triggered by a combination of many molecules, all of which work together and none of which are indispensable

Question 17

What does presynaptic formation require?

Answer 17

–Clustering of synaptic vesicles

–Formation of active zones

Question 18

Describe presynaptic formation fashion;

Answer 18

Presynaptic differentiation occurs in a ‘modular’ fashion, with presynaptic proteins delivered to the site of contact by via pre-assembled vesicular complexes

Question 19

How fast does the clustering of synaptic vessels occur in presynaptic development?

Answer 19

synaptic vesicles appear to be transported along axons in discrete ‘transport packets’that stabilise at sites of contact. Less than 1 hour later, functional release can be detected.

Highly regulated though

Question 20

How is the active zone assembled?

Answer 20

Active zones appear to be assembled by the insertion of pre-assembled vesicles that contain all components of the active zone

–These vesicles then fuse with the presynaptic membrane, forming an active zone at that site

Question 21

What are in the active zone assembly vesicles?

Answer 21

Pre-assembled active zone vesicles were isolated as 80 nm dense core vesicles containing active zone proteins such as Piccolo, Bassoon, syntaxin, SNAP-25

Question 22

What are the assemble vesicles called?

Answer 22

Termed Piccolo Transport Vesicles (PTV’s)

Question 23

How is the PSD formed?

Answer 23

Despite the PSD being made up of scaffolding molecules that form multi-molecular complexes, the PSD is not formed by pre-assembly of these complexes and their trafficking to the site of contact

Rather, components of the PSD appear to be recruited sequentially to postsynaptic sites.

Basically= PSD proteins recruited sequentially

Question 24

Describe what comes first, receptors or scaffold proteins in the PSD;

Answer 24

–Scaffolding molecules such as Shank appear prior to glutamate receptors
–Dynamic imaging of GFP-tagged NMDA and AMPA receptors show that these two subtypes of glutamate receptors do not traffic together

Question 25

Describe AMDA recruitment in the PSD

Answer 25

AMPA receptors are trafficked along microtubules with scaffolding proteins and then recruited from intracellular pools

Question 26

Describe NMDA recruitment in the PSD

Answer 26

NMDA receptors transport in vesicles with some of its binding proteins via a unique route involving dendritic golgi

Question 27

Describe the assembly of proteins into the PTVs;

Exam Q

Answer 27

Proteins made in the ER. Modified in the Golgi. Put into vesicles.

• All the proteins are assembled in the membrane of the vesicles
• Vesicles find site of contact and fuse (kit insertion) creating the active zone

Question 28

Are proteins made at the dendritic processes in PSD?

Answer 28

Neurons sometimes do because the processes are too long for proteins to travel down.

Dendritic golgi take up NMDA receptors and modify them

Question 29

How long does it take for a synapse to form?

Answer 29

However, development of live imaging techniques have shown that individual synapses can form in a matter of hours

Question 30

How is the synapse shown to be semi functional within an hour of forming?

Answer 30

–e.g. evoked vesicular exo-and endocytosis can be demonstrated within 1 hour of axo-dendritic contact.

Question 31

What does IHC show in terms of synapse formation?

Answer 31

–Immunohistrochemical staining of nascent synapses show the presence of presynaptic active zone proteins and the formation of functional presynaptic boutons can form in less than 30 minutes

–Clusters of postsynaptic receptors are first seen on average, another 1 hour later

Question 32

What occurs first pre or post synpatic formation?

Answer 32

–Presynaptic differentiation proceeds more rapidly that does postsynaptic differentiation

Question 33

Compare and contrast pre and post synaptic formations;

Answer 33

Post;
= Sequential recruitment of proteins

Pre;
= PTV there all come down the processes rapidly

Question 34

Are synapses formed rapidly mature?

Answer 34

Synapse formed over this short time frame are far from mature

Hour = crude

• not very plastic
• Some functionality

Question 35

What is presynatic plasticity?????

Answer 35

• Regulation of vesicle release

- Reserve pools

Question 36

How long does maturation really take?

Answer 36

After the rapid formation of active zones and recruitment of synaptic vesicles, longer term maturation of the synapses occurs over many days

Question 37

What occurs in synaptic maturation?

Answer 37

–Transmitter release is fine tuned.
–Synapses acquire large reserve pools of vesicles, required for high frequency release
–Protrusive activity of axonal and dendritic filopodia subsides