Lectures 6, 7, & 8 Flashcards
How does LTP inducing stimulus increase trapping of AMPA receptors?
CAMKII, Stargazing, and PSD-95
What does PSD-95 do to increase AMPA in the synapse?
Form potential slots for trapping AMPA receptors diffusing through the PSD
How does CAMKII increase AMPA receptor number in the synapse?
Phosphorylation stargazin from the membrane to facilitate binding to PSD-95
What does stargazin do to increase AMPA receptor number in the synapse?
Binding of stargazin to PSD-95 traps more AMPA receptors
How do endosomes get activated?
Calcium
What does inhibiting the endosomes in the intracellular pool do?
Reduce LTP by a lot
How does the actin cytoskeleton get degraded?
Ca2+ coming in activates a signaling cascade to degrade the actin skeleton
What happens if you introduce a LFS within 10 minutes of a TBS stimulation?
LTP will be induced but not sustained
To have LTP endure for more than 30 minutes, additional processes must be engaged to create a dendritic spine environment that will….
Prevent endocytotic processes that remove AMPA from the PSD & ensure delivery of a steady supply of synaptic proteins
What is the stabilization phase?
During the 30 min period after LTP induction that involves remodeling of the dendritic spines
Does spine size have a relation with AMPA receptor number in the PSD?
Yes! Large spines can live for days in living animals
Changes in dendritic spine density, size and plasticity underlie ___ ___ due to age
Cognitive changes
What are the two states actin exists in?
F-actin and G-actin
What is the polymerized version of Actin called?
F-Actin
What is the monomer version of Actin called?
G-actin
When phosphorylated, what does cofilin do?
Help F-actin build polymers
What does cofilin do when unphosphorylated?
Severs and depolymerized actin filaments
What happens when you apply a drug that prevents actin polymerization before TBS?
LTP is induced but rapidly decays
What phosphorylates cofilin?
LIMK
What happens if a drug that prevents actin polymerization is applied 15 minutes after TBS?
LTP Is maintained
What returns cofilin back to its unphosphorylated stated?
Slingshot
How are actin filaments connected when not in LTP?
In a meshlike network in the spine head held by inactive CAMKII
What does the neck of the synapse contain?
Bundles of F-actin held together by an inactive CaMKII complex
What happens when CaMKII is activated and detached from F-actin?
Proteins sever the strands into shorter strands and cofilin depolymerized F-actin and prevents them from rejoining
What happens once cofilin is phosphorylated?
Cofilin stops depolymerizing and then the new small F-actin strands rapidly polymerize
How long do the 2-phases of disassembling to rebuilding take?
~30 minutes
What do Cell Adhesion Molecules do to stabilize LTP?
They are proteins that are located on the cell surface and bind with other cells with the ECM
What are the two important cell-adhesion molecules?
Integrin receptors and N-Cadherins
What do integrin receptors do?
Connect the ECM to the actin cytoskeleton
Influx of Ca2+ and induced signal cascades increases integrin in PSD
What do N-Cadherins do?
Facilitate the coupling of pre and post synaptic regions
Increased synaptic activity makes them cluster and help keep the pre and post regions tightly coupled
What are the 3 main phases of stabilization of LTP?
Actin severing, rapid polymerization, cell adhesion
The generation of new proteins is important to the ____ phase of the trace
Consolidation
What does treatment with a protein synthesis inhibitor prior to a TBS do to LTP and induction?
LTP induced but does not last
Long lasting LTP depends on both what?
Local and activity induced signaling of the genome
How does genomic signaling work?
Signaling molecules activated by LTP can lead to new mRNA that can sustain LTP
Signaling molecules enter nucleus and phosphorylated transcription factors that interact with DNA to create new mRNA and proteins to modify synapses
What are the two ways signaling molecules can reach the nucleus?
Synapse to nucleus
Soma to nucleus
Describe the synapse to nucleus signaling pathway
- stim of post synaptic neuron activates secondary messengers
- second messengers activate protein kinases which translocate to the nucleus
- phosphorylation of CREB protein
- CREB initiation transcription of proteins important to synapse
Describe Soma to Nucleus signaling
- APs from LTP induction open vdCCs on membrane of soma
- calcium can signal a number of important events
- within and outside the nucleus leads to CREB phosphorylation
- phosphorylation of CREB protein leads to transcription of important proteins to synapse
