Learning and Memory Flashcards
Why do we learn?
2 types of memory and ellaborate
Declarative learning
- Facts and (memories of) events
- Remembering…
Non-declarative learning- less conscious
- procedural memory: skills and habits (striatum)
- Classical conditioning- skeletal musculature (cerebellum), emotional responses (amygdala)
- …learning to ride a bike
- …the dinner bell makes you hungry
- what is learning?
- what did Donald Hebb (1949) suggest?
- Learning is the response of the brain to environmental events and involves adaptive changes in synaptic connectivity which will in turn alter behaviour.
- Donald Hebb in 1949 suggested a hypothesis for how, through neuronal networks, the brain can process and store information:
“When an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increased”
(theres some change in the connectivity of cell A and B (synapse) → this is causing after what this persistent event is that has cause them to fire, later on now cell A is more able to fire cell B)
Donald Hebb main theory
“Cells that fire together wire together”
Strengthening and weakening synaptic connections in the brain provides a means by which learning occurs and memories can be formed.
Cells that fire together wire together example
Sensory inputs from Grandma processed and converge on a cell in the hippocampus:
converge on the hippocampus
Cell A – sensory input for sight of Grandma
Cell B – sensory input for smell of perfume
Cell B- chopping onions
Initially an individual input (only one cell) might not be sufficient to stimulate the hippocampal neuron- but it will cause an EPSP
(The Excitatory Post Synaptic Potential (EPSP) is not great enough to fire an action potential)
But if you put 2 of these events together (A and B) then those two EPSP’s on each of those neurons might be sufficient in order to cause this hippocampal neuron to fire.
If this association is made repeatedly, the synapses of A and B onto the hippocampal neuron will be strengthened, so that the individual inputs are sufficiently strong to fire the hippocampal neuron, and just the smell or a picture of Grandma is sufficient to recall a complete memory.
On the other hand, she doesn’t have associations of chopping onions with her grandma so this trigger hasn’t converged. It will still cause an EPSP but as its not tied in with A and B it wont trigger the hippocampus in order to give memories about Grandma. - as only cells that wire together fire together
The hippocampus:
- involved in?
- specifically?
- where is it located in humans?
- easy to study in?
- Hippocampus- learning and memory
- associative learning and spatial memory
- Sits in the middle of our brains in humans
- It’s easy to study in mice and rats
Long term potentiation:
- what is it?
- what does the hippocampus allow for?
- where has LTP now been studies?
- mechanism underlying synaptic strengthening
- Hippocampus - shape and anatomy means pathways can be easily distinguished and recorded from electrophysiologically (the architecture of connections of neurons make it easy to study under a microscope)
- LTP has now been studied in most other brain areas too
Explain what Bliss and Lomo (1973) discovered about LTP
They took this architecture and stuck a stimulating electrode into an axonal fields that is projecting in this case into the dentate gyrus. Then they stick electrons in the pyramidal neurons in the dentate gyrus and recorded activity (changes in voltage) in those neurons and this is the EPSP. So they’re measuring the amount of response the dentate gyrus neuron has in response to stimulating this axon.
First of all they would stimulate the neuron once and record the EPSP and then wait a minute or two and do it again and wait a minute or two do it again. When you do this you get quite a stable recording of EPSP and you normalise this being 0 (standard response of those neurons)
After 20 mins they give a high frequency stimulation which leads to response after response so EPSP’s don’t have a chance to go down again. You end up with the charge in this post synaptic neuron reaching a peak where its activated.
Then you stop and go back to what you were doing before and just record one stimulation of this axon at a time into the dentate gyrus. What you find is the dentate gyrus has a much bigger response to the single stimulation so you have strengthened the response of this neuron. So now it doesn’t require high frequency stimulation you just require a single activation and you get this much bigger response in the post synaptic neuron. This response can last for hours.
LTP events which increase the response of the cell.
Recording electrical activity: what is found?
Stimulating axonal projections onto CA1 pyramidal neuron
Phase 1:
- Stimulate A you get a small excitatory post synaptic potential. If you stop and wait for this to go back down to 0, then stimulate B, you’ll get a small postsynaptic potential.
- You’re getting EPSPs from both of these inputs and they’re both small. If you do this over and over again you 0 it.
Phase 2:
- Then you do a high frequency stimulation (100 Hz), tetanic stimulation, so what you see is this big increase in the size of the EPSP
- This is because you’ve added them all together (summated them) and you have a much bigger charge into that synapse of A onto the pyramidal neuron so theres an increased EPSP and this cell is likely to fire.
Phase 3:
- Stop again and now go back to what you were doing before (measuring A vs B)
- Because you were firing A and B separately, A has had that tetanic stimulation. LTP has occurred in A and now when you do the normal stimulation of A and measure its activity you get a bigger EPSP (due to strengthening synapse A because of this high frequency stimulation).
- Because B had an asynchronous stimulation (no stimulation during strong stimulation A), when you go back and look at synapses at B you find theres no LTP.
Recording electrical activity: main events
Temporal summation
Input specific- LTP is input specific to A and not B
What is the Morris Water Maze and what is found?
- Test of spatial learning where you have a paddling pool sized arena full of water and inside it you put a platform thats underneath the water and can’t be seen. A rat is put in the water.
- The rat uses things in the environment to work out where it is. It swims around and tries to escape this water until it finds platform
- Once it gets on the platform it is taken out, dried off and a few hours later it might get put in.
- If this is tested repeatedly, you’ll put the rat in and it will swim straight to the platform.
- It learns where the platform is based on spatial cues in the environment
Findings from Morris Water Maze in control and rat with hippocampal lesion
Control rat:
- First trial: long length of the path and time it takes to find the platform is very long.
- After 10 trials: rat swims straight to platform
Rat with hippocampal lesion:
- First trial: takes about the same time to find platform as control
- After 10 trials: rat hasn’t learnt anything- it still spends the session trying to fins the hidden platform
This tells us that the hippocampus appears to be essential for learning and memory and those LTP experiments were in the right place for this kind of learning and memory
What do probe trials for the Morris Water Maze do and find?
Split the pool into quadrants and see how long each rat spends in the target quadrant (where the platform should be) vs the non-target quadrant.
Findings:
Control: spending significantly more time in the target quadrant
Hippocampal lesioned rat: spending equal time in the target and non-target quadrant
What is the important neurotransmitter for LTP?
Glutamate
What is found at normal neuronal transmission?
- glutamate is released from pre-synaptic terminal and it lands on different types of glutamate receptor in the post synaptic terminal (AMPA and NMDA)
- glutamate will bind to AMPA receptor, AMPA rceptor will open a channel and you’ll get a flux of Na+ into the post-synaptic neuron
- glutamate may also bind to the NMDA receptor but under baseline conditions, the normal resting membrane potential, theres a Mg that sitting inside the channel which is blocking movement of ions through the NMDA channel
- so only getting EPSP through the AMPA receptors
What is found at postsynaptic membrane in excited state?
- resting membrane potential will have been shot up and membrane is going to be depolarised
- as a result, that magnesium is going to get ejected out of that NMDA receptor
- if glutamate is released onto this depolarised membrane, it still does the same thing to the AMPA receptor but at the same time it is able to activate NMDA receptors.
- The channel opens, the magnesium has been kicked out and you get an influx of calcium and sodium into the postsynaptic neuron.
- Calcium has double the positive to sodium so your getting a much bigger EPSP
- NMDA is only activated in these depolarised neurons
Role of NMDA in LTP and learning (findings for Morris Water Maze task)
They did Morris water maze but while they were doing the learning, they injected an NMDA receptor antagonist into hippocampus of rats and then did Morris Water maze training
If you did probe trial at the end: the control rats who were given a saline injection spent the whole probe trial swimming around the target quadrant because they knew where the platform should be
Rats injected with AP5 (NMDA receptor antagonist) spend an equal amount of time in all quadrants (it was like they had no hippocampus)
This tells us that NMDA receptor activity in hippocampus is important for this spatial learning
Traces from this paper looking at LTP with high frequency tetanic - so get the baseline do the high frequency stimulation and then measure activity in the hippocampus again in the same way you were doing at baseline, then do another high frequency stimulation and do the same thing again. At connections wheres theres high frequency stimulation you have much bigger EPSPs occurring than you did under the normal conditions before the stimulation occurred. If you put AP5 into this, you do the high frequency stimulation but after you do that and go back to normal recording levels the response of the cells goes back to how it was previously at baseline.
Sum of what is found with NMDA antagonist in Morris Water Maze task?
No evidence of learning or LTP
Whats happening at the synapse for Glutamate release onto inactive cell
(membrane at resting potential)
- AMPA receptor activated to create EPSP
- NMDA receptor blocked by Mg2+ ion
- Depolarization from AMPA activation
- not sufficient to expel Mg2+
