Is LTP underlying learning?

Question 1

What is the Morris water maze?

Answer 1

there is a pool of water, with a hidden platofrm

place the animal in the water, give it cues and measure how quick it learns to find the platform

Question 2

What happens after learning in the morris water maze?

Answer 2

Controls - find the platform quickly

Lesioned hippocampus rats - can’t learn where the platform is

Question 3

What are probe trials and what do they reveal?

Answer 3

Once they have learnt the location, take the platform out and measure how long they spend in each quadrant

controls - spend lots of time in the quadrant it was in
lesions - spend equal time everywhere

Question 4

What is the role of NMDA in LTP and learning?

Answer 4

If you give an NMDA antagonist (AP5), there is no evidence of learning where the platform is

If trying to do LTP with HFS, in presence of NMDA antagonist, there is no change in the EPSP after - shows that it is essential for learning and memory

Question 5

Is LTP are real and physiological phenomena?

Answer 5

Tetanic stimulation in rat hippocampus is not how people are actually functioning in real life

Question 6

How can you look at the brains of humans?

Answer 6

Neuroscientists remove tissue from the brain when removing a tumour, will sometimes remove healthy tissue. They have a lab set up close to the hospital room, and examine it

Question 7

Are studies on animals relevant to humans?

Answer 7

An experiment was done where they looked at human inferotemporal cortex which was removed during surgery - HFS produced LTP and LFS produced LTD - cause the exact same in humans as rats and not just specific to hippocampus

Question 8

Is there an equivalent of tetanic stimulation?

Answer 8

Yes, Theta waves

Question 9

Why is tetanic stimulation problematic?

Answer 9

It is artificially high stimulation

Question 10

What are theta waves?

Answer 10

Rhythms of activity you see across brains areas - waves of neuronal activity

Question 11

What do hippocampal theta waves do?

Answer 11

Accompanies behaviours when the animal is active - running swimming, head movements, plays a role in synchronising activity in different brain regions

Question 12

What happens if you do electrical stimulation at the same time as a theta wave is occurring?

Answer 12

If you stimulate the neuron at the peak of a wave it generates LTP

If you stimulate the neuron at the trough it generates LTD

Things in the environment are causing the neuron to be stimulated - during a peak, things are strengthened

Question 13

What do theta waves cause?

Answer 13

The physiological change in hippocampus for LTP to occur - creating the environment where LTP is occurring

Question 14

What do disruptions in theta waves cause?

Answer 14

Deficits in learning tasks that are similar to those caused by hippocampal lesions

Question 15

Can you manipulate LTP?

Answer 15

Yes, you can boost it to enhance memory or vice versa

Question 16

How can you manipulate LTP?

Answer 16

Genetically - increase the amount of a subtype of the NMDA receptor (NR2B) - leads to enhanced LTP and there is a significant increase in how they learn in the maze task. When you mess up LTP, hard to improve performance

Question 17

What is one something which decreases memory and LTP?

Answer 17

Age - peak learning and memory in young adulthood, then get a cognitive decline
Rat study - 4 vs 24 mongths
Performance - young learn where platform is very quick, old can do it but takes longer.
LTP - big EPSP change, double in young mice, dramatically reduced in older
NMDA - decreased expression of 2 subunits of the NMDA receptor

Question 18

How can you enhance LTP?

Answer 18

Enrichment - living in standard environment vs enriched
Enriched promotes the processes in the brain leading to plasticity
Enhanced acquisition in Morris water maze - find it a lot quicker
Increased LTP signal (not due to AP5) - enhancement of LTP

Question 19

Can you reverse the effects of ageing?

Answer 19

Task: mice perform a task, errors are how bad they learnt it
3 environments, 2 ages
Young - irrespective of environment, learn task the same
Old - standard vs enriched no difference, but impoverished show greater deficits
took mice and changed environment, left for 6 weeks
remained impoverished: not worse
impoverished into enriched - dramatic increase, but not as good as people in condition all along
enriched into impoverished - decrease in performance

Question 20

What do the reversal of negative effects of the environment show?

Answer 20

That we need to look at elderly people and where they are living as it impacts their cognitive health

Question 21

How does associative LTP work?

Answer 21

Weak synapse: activation does not lead to AP
Strong synapse: activation leads to AP
Repeatedly stimulate the 2 pathways together - depolarisation from strong synapse leads to removal of Mg from NMDA receptors - LTP
This strengthens the weak synapse - activates same stimulus, but will get a stronger response

Question 22

How does LTP relate to real life in associative learning?

Answer 22

Aversive event - loud noise - is a strong stimulus, leading to fear

Tone is a weak stimulus, become stronger but only if weak and strong are active at the same time and if there is depolarisation of the post-synaptic neuron

Question 23

Where is the fear conditioning pathway?

Answer 23

In the amygdala - converges all of the sensory information, if they are activated together, controls the motor output (response)

Question 24

What synaptic connections occur in the amygdala?

Answer 24

Strong input from the US (shock) leads to depolarisation of the post synaptic cell

Weak input from the CS (tone) is strengthened by postsynaptic depolarisation leading to activation of NMDA receptors, leading to LTP of this synapse

Question 25

What is the problem with associative studies?

Answer 25

Looks at the correlations between LTP and memory, but no cause

Question 26

What is opigenetics?

Answer 26

The way that we can control cells by shining lights on them

Question 27

How does opigenetics work?

Answer 27

Can implant neurons into areas of the brain, with receptors modified to respond to light and activate them under different conditions - activating receptors directly on neurons

Question 28

Example of optigenetics - fear conditioning

Answer 28

Pair an US with the light which has been shined (weak synapse)
Performance is trying to get food but pressing a lever, but they stop responding when they get electric shock
When paired, they start freezing, replace neutral stimulus with our own control. The synapses are strengthened in the same way, shine a light and can stimulate it alone because it has been strengthened

Question 29

What happens in you invoke LTP or LTD?

Answer 29

it strengthens or weakens the memory - only occurs after paired conditioning - can change it so it forgets what happens, just by firing light onto the brain

Question 30

What does increasing NMDA function in the forebrain lead too?

Answer 30

Enhanced spatial memory - mice with NMDA NR2B receptor in, performed better than normal mice in more water maze - only need to do it for people who are cognitively impaired, doing it on healthy brain doesn’t make much difference

Question 31

Do we need to search for cognitive enhancers?

Answer 31

No - are we smart enough already?
We might remember too much, we need to filter important stuff and balance of LTP and LTD to be healthy - need to look at cognitive impairments
also, too much glutamate is excitotoxic