LTP Flashcards
Define learning
The process of acquiring new information
Define memory
The persistence of learning
OR
The storage and retrieval of previously learned information
What are the two main forms of long term memory?
Declarative (knowing what)
Procedural (knowing how)
What is declarative memory split into?
Semantic
Episodic
What is synaptic plasticity?
A neurons ability to cause a persistent change in the synaptic strength
When does synaptic plasticity occur?
Development
Learning and memory
Ageing
Response to trauma and disease
Who discovered LTP?
Bliss and Lomo 1973
What are the 4 classical properties of LTP?
Persistence
Cooperativity
Associativity
Specificity
How did Bliss and Lomo discover LTP?
Repeated stimulation of the peforant path (same as the Schaffer collateral) they noted an increased response from the same level of stimulation
What is meant by “specificity” in LTP?
Specific to tetanised pathways
Non-tetanised inputs are not potentiated
What is meant by co-operativity?
There is an intensity threshold
What is meant by associativity?
Weak input will potentiate IF a strong convergent input is activated at the same time
(Classical conditioning)
What effect does classical conditioning have on synaptic strength?
If a weak conditioned stimulus causing firing at the same time as a strong unconditioned stimulus, there is increased synaptic strength of the weaker stimulus
What stimulation patterns can be used to induce LTP?
Tetanic stimulation (100Hz for 1 second, robust, not physiological)
Theta-burst stimulation (short burst @ 5 Hz, physiological)
Primed burst
Realistic stimulation
What are the main phases of LTP?
(Post-tetanic potentiation)
Early
Intermediate
Late
Which receptor types are vital for LTP?
NMDAR
even though AMPAR needed for immediate activation, NMDAR needed to carry the signal on
Outline what the 3 main stages of LTP are
1 - post-translational modifications
2 - mRNA translations
3 - protein synthesis and gene transcription
Use what u got whilst the rest is cookin
What occurs during the first phase of LTP?
AMPAR activation causes Ca2+ influx
Phosphorylates and activates membrane proteins
This recruits more AMPAR to the membrane
When does the early phase of LTP occur?
Within 1 hour of stimulation
What occurs during phase 2 of LTP?
Synthesis of new proteins from exsiting mRNA
Increased mRNA translation
When does phase 2 of LTP occur?
Within 3 hours of stimulation
What occurs during stage 3 of LTP?
Gene transcription occurs to create new mRNA and synthesis new proteins
When does phase 3 occur?
3 hours after stimulation
How was LTP disocvered to be in 3 diff phases?
When given ansiomycin this blocks mRNA translation to protein the increased transmission increases for approx. half an hour then loss of activity and the fEPSP returned to baseline
When given actinomycin D, transcription is blocked, there was increased activity and sustained increase for up to 100 mins and then loss of activity and then return to baseline
(Draw this)
Which group of enzymes are required for phase I LTP?
Kinases
Which group of enzymes are required for LTD?
Phosphatases
Phosphorylation of GluA1 at which position causes LTP?
ser831
Phosphorylation of GluA2 at which position causes LTD?
ser845
Outline the process of LTD
Lower sustained activity Moderate calcium De phosphorylation Decreased conductance Decreased AMPAR trafficking
What evidence is there that GluA receptors traffic during LTP?
Immunohistochemical detection of surface GluA receptors and imaging of fluorescent tags show an increased number
What are TARPs?
Transmembrane AMPAR regulatory proteins
What is the role of TARPs?
Modulate AMPAR trafficking and lateral surface diffusion of AMPARs
Modulate biophysical properties of AMPARs
What are the three main ways to increase post-synaptic receptor numbers?
Increase receptor delivery
Lateral diffusion
Reduce removal of receptor
The mRNA for which kinases are present in dendrites?
MAP2
CamKII
What is MAP2?
Microtubule-associated protein 2
Modulator of microtubules dynamics and growth
What is CamKII?
A subunit involved in NMDAR-dependent signalling
Which mechanisms may lead to increased protein synthesis in phase II?
Inhibition of mRNA degradation
Phosphorylation of ribosomal proteins triggered by ERK
What activates gene transcription?
Transcription factors binding to specific target sites in the genome
Can either increase or decrease receptor function
What are the two types of TF?
Constitutive
Inducible
What is a constitutive TF?
Inactive and present in cytoplasm
Gets activated later
Eg CREB, Elk1, NFkappaB
What is an inducible TF?
Activated by constituve TFs and then go on to transcribe their own target
Eg zif268, junB
(IEGs)
How does CREB alter gene transcription?
Binds to cAMP response elements in the DNA which then dictate whether there is up or downregulation of transcription
Outline the how IEGs are involved in LTP
Ca2+ actives kinases
Kinases enter nucleus to cause phosphorylation of TFs
IEGs bind to DNA to and induces transcription
GluRs created and AMPAR trafficked to the membrane
How do we know that CaMKII is relevant to NMDAR signalling?
KO mice show much lower amplitude than WT
What are the two mechanisms through which early synaptic plasticity is maintained?
Phosphorylation and trafficking of receptors
How can lateral diffusion of receptors be observed?
With quantum dots
Does zif268 induction cause LTP?
It is needed for late LTP
Which late response genes are involved in LTP?
CREB targets: BDNF
NFkB targets: neuronal cell adhesion molecule (NCAM)
zif68 targets: proteasome genes, agrin
What does NCAM do?
Promotes neurite outgrowth and maintenance of synaptic architecture
What does persistence mean in terms of LTP?
Memory outlasts the induction of LTP
