LTP

Question 1

Define learning

Answer 1

The process of acquiring new information

Question 2

Define memory

Answer 2

The persistence of learning
OR
The storage and retrieval of previously learned information

Question 3

What are the two main forms of long term memory?

Answer 3

Declarative (knowing what)

Procedural (knowing how)

Question 4

What is declarative memory split into?

Answer 4

Semantic

Episodic

Question 5

What is synaptic plasticity?

Answer 5

A neurons ability to cause a persistent change in the synaptic strength

Question 6

When does synaptic plasticity occur?

Answer 6

Development
Learning and memory
Ageing
Response to trauma and disease

Question 7

Who discovered LTP?

Answer 7

Bliss and Lomo 1973

Question 8

What are the 4 classical properties of LTP?

Answer 8

Persistence
Cooperativity
Associativity
Specificity

Question 9

How did Bliss and Lomo discover LTP?

Answer 9

Repeated stimulation of the peforant path (same as the Schaffer collateral) they noted an increased response from the same level of stimulation

Question 10

What is meant by “specificity” in LTP?

Answer 10

Specific to tetanised pathways

Non-tetanised inputs are not potentiated

Question 11

What is meant by co-operativity?

Answer 11

There is an intensity threshold

Question 12

What is meant by associativity?

Answer 12

Weak input will potentiate IF a strong convergent input is activated at the same time

(Classical conditioning)

Question 13

What effect does classical conditioning have on synaptic strength?

Answer 13

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

Question 14

What stimulation patterns can be used to induce LTP?

Answer 14

Tetanic stimulation (100Hz for 1 second, robust, not physiological)
Theta-burst stimulation (short burst @ 5 Hz, physiological)
Primed burst
Realistic stimulation

Question 15

What are the main phases of LTP?

Answer 15

(Post-tetanic potentiation)
Early
Intermediate
Late

Question 16

Which receptor types are vital for LTP?

Answer 16

NMDAR

even though AMPAR needed for immediate activation, NMDAR needed to carry the signal on

Question 17

Outline what the 3 main stages of LTP are

Answer 17

1 - post-translational modifications
2 - mRNA translations
3 - protein synthesis and gene transcription

Use what u got whilst the rest is cookin

Question 18

What occurs during the first phase of LTP?

Answer 18

AMPAR activation causes Ca2+ influx
Phosphorylates and activates membrane proteins
This recruits more AMPAR to the membrane

Question 19

When does the early phase of LTP occur?

Answer 19

Within 1 hour of stimulation

Question 20

What occurs during phase 2 of LTP?

Answer 20

Synthesis of new proteins from exsiting mRNA

Increased mRNA translation

Question 21

When does phase 2 of LTP occur?

Answer 21

Within 3 hours of stimulation

Question 22

What occurs during stage 3 of LTP?

Answer 22

Gene transcription occurs to create new mRNA and synthesis new proteins

Question 23

When does phase 3 occur?

Answer 23

3 hours after stimulation

Question 24

How was LTP disocvered to be in 3 diff phases?

Answer 24

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)

Question 25

Which group of enzymes are required for phase I LTP?

Answer 25

Kinases

Question 26

Which group of enzymes are required for LTD?

Answer 26

Phosphatases

Question 27

Phosphorylation of GluA1 at which position causes LTP?

Answer 27

ser831

Question 28

Phosphorylation of GluA2 at which position causes LTD?

Answer 28

ser845

Question 29

Outline the process of LTD

Answer 29

``` Lower sustained activity Moderate calcium De phosphorylation Decreased conductance Decreased AMPAR trafficking ```

Question 30

What evidence is there that GluA receptors traffic during LTP?

Answer 30

Immunohistochemical detection of surface GluA receptors and imaging of fluorescent tags show an increased number

Question 31

What are TARPs?

Answer 31

Transmembrane AMPAR regulatory proteins

Question 32

What is the role of TARPs?

Answer 32

Modulate AMPAR trafficking and lateral surface diffusion of AMPARs Modulate biophysical properties of AMPARs

Question 33

What are the three main ways to increase post-synaptic receptor numbers?

Answer 33

Increase receptor delivery Lateral diffusion Reduce removal of receptor

Question 34

The mRNA for which kinases are present in dendrites?

Answer 34

MAP2 | CamKII

Question 35

What is MAP2?

Answer 35

Microtubule-associated protein 2 | Modulator of microtubules dynamics and growth

Question 36

What is CamKII?

Answer 36

A subunit involved in NMDAR-dependent signalling

Question 37

Which mechanisms may lead to increased protein synthesis in phase II?

Answer 37

Inhibition of mRNA degradation | Phosphorylation of ribosomal proteins triggered by ERK

Question 38

What activates gene transcription?

Answer 38

Transcription factors binding to specific target sites in the genome Can either increase or decrease receptor function

Question 39

What are the two types of TF?

Answer 39

Constitutive | Inducible

Question 40

What is a constitutive TF?

Answer 40

Inactive and present in cytoplasm Gets activated later Eg CREB, Elk1, NFkappaB

Question 41

What is an inducible TF?

Answer 41

Activated by constituve TFs and then go on to transcribe their own target Eg zif268, junB (IEGs)

Question 42

How does CREB alter gene transcription?

Answer 42

Binds to cAMP response elements in the DNA which then dictate whether there is up or downregulation of transcription

Question 43

Outline the how IEGs are involved in LTP

Answer 43

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

Question 44

How do we know that CaMKII is relevant to NMDAR signalling?

Answer 44

KO mice show much lower amplitude than WT

Question 45

What are the two mechanisms through which early synaptic plasticity is maintained?

Answer 45

Phosphorylation and trafficking of receptors

Question 46

How can lateral diffusion of receptors be observed?

Answer 46

With quantum dots

Question 47

Does zif268 induction cause LTP?

Answer 47

It is needed for late LTP

Question 48

Which late response genes are involved in LTP?

Answer 48

CREB targets: BDNF NFkB targets: neuronal cell adhesion molecule (NCAM) zif68 targets: proteasome genes, agrin

Question 49

What does NCAM do?

Answer 49

Promotes neurite outgrowth and maintenance of synaptic architecture

Question 50

What does persistence mean in terms of LTP?

Answer 50

Memory outlasts the induction of LTP