week 2 - long term potentiation

Question 1

Describe Morice et al. (2008) Learning and memory study

Answer 1

mice with a downsyndrome model vs wild type

Mice with downsyndrome have less synaptic plasticity

Question 2

Where is the hippocampus?

Answer 2

In the medial temporal lobe

Question 3

What is another reason why the hippocampus is widely studied in learning and memory

Answer 3

Because it is very easily accessed electrophysiologically

You can even remove it from the brain and it’ll stay alive for much longer than other areas

Question 4

What is anterograde amnesia

Answer 4

Inability to form new memories

Question 5

What is retrograde amnesia

Answer 5

Loss of old memories

Question 6

What is an intepretation of the fact that most hippocampal damage leads to amnesia of recent memories or new memories

Answer 6

Memories might start off in the hippocampus and move elsewhere

Question 7

Describe frankland and bontempi (2005) ‘s study on hippocampal lesions

Answer 7

Hippocampal lesions impair memory in rodents in a time dependent way

Memory created in rodents

When hippocampus is lesioned soon after the memory is created the memory is lost

When hippocampus is lesioned after a month after the memory, the memory is generally not lost

This suggests that memories start in the hippocampus and move elsewhere

Question 8

Describe Neves, Cooke and Bliss’s study into hippocampus circuitry

Answer 8

Most the input to the hippocampus comes into the dentate gyrus, flows to CA3 and flows to the hippocampus

The flow of information into the hippocampus in rodents is very simple

This is another reason why the hippocampus is a widely studied structure

Question 9

How can you differentiate synaptic potentials and action potentials in the hippocampus in rodent hippocampal studies

Answer 9

Use a simple lamination (research more about this)

Because the hippocampus is simple, you can interpret what is synaptic vs. what is hippocampal, as well as being able to visualize the discrete fibre pathways

Question 10

Describe a transverse hippocampal slice and why is this better in the hippocampus

Answer 10

You can look down at a slice of the rodent hippocampus and see the structure of the neural pathways

You can see what’s CA1, CA3 and you can stimulate different bits

This is better in the hippocampus cus in other brain areas the pathways cross over each other so you can’t isolate the different responses

Question 11

What predictions would hebbian plasiticty theory generate - Q1

Answer 11

Activity dependence - Modification of synsapses requires co-activity between pre and post synaptic neurons

input specifity- only inputs co-active with the post synaptic cell will undergo modification

Cooperativtiy - Multiple inputs are required to drive plasticity inducing post-synaptic depolarization

Associativity - Weak inputs that are unable to depolarize the cell sufficiently enough, will still undergo change if paired with strong depolarizing inputs

Longetivty - Phenomenons should be long-lasting if they are going to serve memory

Question 12

Describe intracellular vs. extracellular recording and benefits

Answer 12

Intracellular - inside the neuron. EPSP’s can be measured
Benefits = low noise recording from individual neurons

Extracellular - Away from the neuron e.g eeg

Question 13

How does the steepness of the EPSP slope correlate with synaptic strength?

Answer 13

The steeper the slope of the EPSP field recording, the stronger the population synapses

Question 14

Describe Bliss and Lomo’s 1973 LTP study

(Q1- Activity dependence)

Answer 14

Looked in the dentate gyrus recieving input
Recorded from a population of excitatory neurons in a aneastetised rabbit

One neuron stimulated and one recorded in each hemisphere

One hemisphere recieved high frequency electrical stimulation, the other recieved low frequency control pulses

Only the hemisphere that has been stimulated undergone LTP

LTP was measured as the field EPSP

This shows high frequency stimulation were required for increased synaptic strneght

This also shows that plasticity is activity dependent

Question 15

How would you use intracellular recording to measure LTP (markram, 1997)

Q1 - Activity dependence

Answer 15

You can use spike timing dependent plastictiy

Stimulate with a single pulse the presynaptic input at the same time injecting the post synaptic neuron with current

If the presynaptic input is stimulate just before teh post synaptic cell we get a long term potentiation

The close the two stimulatoins are to being simultaneous, the stronger the LTP

Stimulating the post synaptic neuron first before the pre neuron leads to LTD - weakening of synapses

This shows timing of stimuli is important for LTP

This also shows activity is activity depndent

Question 16

How would you demonstrate input specifity for synaptic plasticiy (beck et al, 2000)

(Q1 - Input plasticity)

Answer 16

tetanised vs. non tetanised input

Do more research on this (beck et al, 2000)

Question 17

How would you demonstrate cooperativity and associativity in hebbian plasticity (Q1)

(McNaughton et al, 1978) Mcnaughton, 2003,

Barrioneuvo and brown, 1983

Answer 17

Provide both strong and weak electrical stimulation into the post synaptic neuron

If you stimulate just weak input, no LTP for that synapse

If both strong and weak input is stimulated, you do get LTP for the weak input synapse

Question 18

How would you measure longetivity in hebbian plasticity (Q1)

Abraham et al 2002

Answer 18

Induced LTP in dente gyrus of rat by many stimulations

LTP lasted for 100 days in a rat

LTP even lasted for one rat 360 days, this is half of the rats life

Question 19

What is the relationship between protein synthesis and LTP

Scharf et al, 2002 provided evidence, describe

Answer 19

Protein synthesis

Scharf et al found that if you block protein synthesis, LTP only lasts for an hour then returns back to baseline

If you don’t block protein synthsis, LTP is long lasting

Question 20

What is the synaptic tagging hypothesis

Frey and morris 1998

Answer 20

New proteins get synthesised becasue genes are being expressed

However, because plasitcity is neuron specific, how do you ensure that the proteins only go to the relavent neurons?

Synaptic tag hypothesis = Porteins get sent out all throughout the neuron, but you have a tag/binding partner at the synapses that have recently undergone change

Question 21

WHat is the stages of LTP

Answer 21

Induction - the moment of change when the tetanus has been delivered, steep EPSP slope

Expression - Something in the synapse has changed

Maintenence - Maintenence of the synapse strength

Question 22

What is the mechaism that detects induction (the special condition at which hebbian plasticity occurs) in glutamate synapses

Answer 22

The NMDA receptor is nessercary for the induction of LTP

Most synaptic potential comes in through AMPA receptors (in glutamatergic synapses)

NMDA is voltage gated meaning it only opens at a particular voltage. Normally magnesium is blocking the receptor but when theres enough voltage the magnesium leaves allowing a sharp influx of positively charged calcium ions

Question 23

described NMDA receptors in resting and weakly stimulated vs strongly stimulated synaptes. (detecting expression)

How is this discovered experimentally

Answer 23

resting state = nmda closed
Weakly stimulated = nmda closed
Strongly stimulated = nmda opens

Experimentally, you can use drugs to block the different receptors and look at the effects

Question 24

Describe collingridge et al (1983) NMDA receptor antagonist experiment

(ltp expression)

Answer 24

Used a drug AP5 into the cell bath whilst LTP was being induced

ap5 is a receptor antagonist

When ap5 was in bath, ltp didnt take place

When ap5 was washed away, ltp could take place

This shows that ap5 is nmda receptor dependent

Question 25

Describe effects of NMDA antagonist on morris water maze performance

Morris et al, 1986

(ltp maintence)

Answer 25

When NMDA antagonists are used (injecting ap5 into hippocampus), performance on the morris water maze is strongly impaired

This shows that ltp is nmda dependent

It also shows that morris water maze performance is dependent on LTP

Question 26

What impacts how strong the LTP is, when it happends

shepherd and hungair, 2007

Answer 26

AMPA receptors

You can use dominant negative system to block ampa receptor insertion

Do more research on this

Question 27

Describe Rumpel et al 2005 study on AMPA and LTP

Answer 27

LTP is prevented by blocking ampa receptor insertion

Do more research on this

Question 28

What is an inhibitory avoidace test

Answer 28

Uses operant conditioning

Mice have two compartment, one well lit and one dark

They want to go in the dark but they get a shock when they go in the compartment

If they stay in the light then they have a powerful memory of the electric shop

Question 29

Describe mitsushima et al,s 2011 study

Answer 29

Learning is blocked by insetion of modified dominant negative ampa receptor tail

do more reserach on this

Question 30

Describe PKMzeta as a mechanism for maintenence

sacktor, 2011

Answer 30

By phosphorylating ampa receptor you can change their conductance

PKMzeta is a consituent of a kinase that phosphorylates

if pkm is translated into being a functional kinase, it interacts with ampa insertion mechanisms to promote the insertion of ampas

Most synampses translationally repress PKM. When NMDA is activated and LTP occurs, the block of translation of PKM is lifted

This leads to a positive feedback loop where it supresses the blockade so the maintanence mechanism is continually being expressed at the synapse

Question 31

Describe pastalkovaa et al 2006 study on pkmzeta and rat memory task

(for LTP maintence)

Answer 31

PKMzeta is required for hippocampus dependent memory

Do more research

Question 32

describe Whitlock et al 2006 - learning induced synaptic potentiation occludes LTP

Answer 32

do more research on this