Lecture 20; Synapse Plasticity 2 Flashcards
Describe the changes in energy phase during synaptic transmission;
Electrical AP is converted into Chemical Potential then back to electrical AP
What is crucial to synaptic function?
The synaptic density proteins must be in the right place at the right time in the pre and post synaptic clefts
Describe mature synapses;
High specialised complex structures
What are the three main phases of synaptic development?
Phase 1. Contact between axon and dendrite
Phase 2. Induction of synaptic differentiation
Phase 3. Maturation of developing synapses
Describe what happens initially when neurons differentiate;
phase one
They extend processes called neurites.
Specific processes occur to determine if neurites become axons or dendrites
What determines the route of growth for a neurite?
Phase One
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
What is the function of the growth cone?
Phase One
it is specialised to charter new territory for neurite elongation
What role do filopodia have?
Phase One
•Filopodia constantly extend and retract from the lamellipodium, searching the environment until its attachment leads to neurite extension and outgrowth in that direction.
What can initiate the formation of the synapse?
Phase One
- 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
In reality what is more likely to create a synapse? axon or dendrite?
Phase One
Dendrites are more likely;
– numerous synaptic contacts formed during development are located on dynamic dendritic growth cones and filopodia
How do dendrite filipodia differ from axonal ones?
Phase One
Dendritic filopodia display highly dynamic protrusive behaviour and induce the formation of presynaptic terminals along axonal shafts
What happens at the site of dendritic or axonal contact?
Axonal and dendritic compartments at the contact site differentiate into a presynaptic bouton and a postsynaptic receptive apparatus
Describe what is happening when the dendritic and axonal compartments connect?
Bridges form across the synapse to draw receptors in together
Prior to synapse differentiation, receptors wonder aimlessly around the membrane.
What sends signals to cluster NMDA receptors?
Ephrin
What signals for synapse differentiation?
–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
Whats the reality of synapse differentiation molecules?
Induction likely triggered by a combination of many molecules, all of which work together and none of which are indispensable
What does presynaptic formation require?
–Clustering of synaptic vesicles
–Formation of active zones
Describe presynaptic formation fashion;
Presynaptic differentiation occurs in a ‘modular’ fashion, with presynaptic proteins delivered to the site of contact by via pre-assembled vesicular complexes
How fast does the clustering of synaptic vessels occur in presynaptic development?
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
How is the active zone assembled?
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
What are in the active zone assembly vesicles?
Pre-assembled active zone vesicles were isolated as 80 nm dense core vesicles containing active zone proteins such as Piccolo, Bassoon, syntaxin, SNAP-25
What are the assemble vesicles called?
Termed Piccolo Transport Vesicles (PTV’s)
How is the PSD formed?
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
Describe what comes first, receptors or scaffold proteins in the PSD;
–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
Describe AMDA recruitment in the PSD
AMPA receptors are trafficked along microtubules with scaffolding proteins and then recruited from intracellular pools
Describe NMDA recruitment in the PSD
NMDA receptors transport in vesicles with some of its binding proteins via a unique route involving dendritic golgi
Describe the assembly of proteins into the PTVs;
Exam Q
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
Are proteins made at the dendritic processes in PSD?
Neurons sometimes do because the processes are too long for proteins to travel down.
Dendritic golgi take up NMDA receptors and modify them
How long does it take for a synapse to form?
However, development of live imaging techniques have shown that individual synapses can form in a matter of hours
How is the synapse shown to be semi functional within an hour of forming?
–e.g. evoked vesicular exo-and endocytosis can be demonstrated within 1 hour of axo-dendritic contact.
What does IHC show in terms of synapse formation?
–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
What occurs first pre or post synpatic formation?
–Presynaptic differentiation proceeds more rapidly that does postsynaptic differentiation
Compare and contrast pre and post synaptic formations;
Post;
= Sequential recruitment of proteins
Pre;
= PTV there all come down the processes rapidly
Are synapses formed rapidly mature?
Synapse formed over this short time frame are far from mature
Hour = crude
- not very plastic
- Some functionality
What is presynatic plasticity?????
- Regulation of vesicle release
- Reserve pools
How long does maturation really take?
After the rapid formation of active zones and recruitment of synaptic vesicles, longer term maturation of the synapses occurs over many days
What occurs in synaptic maturation?
–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
