Is LTP underlying learning? Flashcards
What is the Morris water maze?
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
What happens after learning in the morris water maze?
Controls - find the platform quickly
Lesioned hippocampus rats - can’t learn where the platform is
What are probe trials and what do they reveal?
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
What is the role of NMDA in LTP and learning?
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
Is LTP are real and physiological phenomena?
Tetanic stimulation in rat hippocampus is not how people are actually functioning in real life
How can you look at the brains of humans?
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
Are studies on animals relevant to humans?
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
Is there an equivalent of tetanic stimulation?
Yes, Theta waves
Why is tetanic stimulation problematic?
It is artificially high stimulation
What are theta waves?
Rhythms of activity you see across brains areas - waves of neuronal activity
What do hippocampal theta waves do?
Accompanies behaviours when the animal is active - running swimming, head movements, plays a role in synchronising activity in different brain regions
What happens if you do electrical stimulation at the same time as a theta wave is occurring?
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
What do theta waves cause?
The physiological change in hippocampus for LTP to occur - creating the environment where LTP is occurring
What do disruptions in theta waves cause?
Deficits in learning tasks that are similar to those caused by hippocampal lesions
Can you manipulate LTP?
Yes, you can boost it to enhance memory or vice versa
How can you manipulate LTP?
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
What is one something which decreases memory and LTP?
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
How can you enhance LTP?
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
Can you reverse the effects of ageing?
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
What do the reversal of negative effects of the environment show?
That we need to look at elderly people and where they are living as it impacts their cognitive health
How does associative LTP work?
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
How does LTP relate to real life in associative learning?
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
Where is the fear conditioning pathway?
In the amygdala - converges all of the sensory information, if they are activated together, controls the motor output (response)
What synaptic connections occur in the amygdala?
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
What is the problem with associative studies?
Looks at the correlations between LTP and memory, but no cause
What is opigenetics?
The way that we can control cells by shining lights on them
How does opigenetics work?
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
Example of optigenetics - fear conditioning
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
What happens in you invoke LTP or LTD?
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
What does increasing NMDA function in the forebrain lead too?
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
Do we need to search for cognitive enhancers?
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
