Modern Questions For Learning Memories? Flashcards
What helps you to learn good from bad? What do sensory inputs allow you to do? And what helps us to predict the future?
You need an evaluator modulator to learn good from bad
These write the locations of memories
Sensory inputs allow you access certain locations of memories
Memories allow for the future to be predicted.
Describe the food bell dog conditioning pathway:
Food is an unconditioned stimulus
Before the bell is rung and associated with food, it is a neutral stimulus
Ringing it whenever food is about causes it to be a conditioned stimulus
The nervous system tries to use the conditioned stimulus to tell the future, the dog starts salivating
Flies, odours and electric shocks:
Odours and electric shocks can be linked
Flies can avoid odours linked to an electric shock
In olfaction. What is the third order neurones in drosophila?
They are kenyon cells
They receive input from multiple projections neurones (second order in droso) and require simultaneous inputs to fire
They turn a dense combinatorial code into a sparse selective code.
How kenyon cells does an odour activate? How are kenyon cells in drosophila related to reward? How many kenyon cells respond to an odour?
Each odour activates a few kenyon cells. Kenyon cell sample very small regions of space.
Kenyon cells also need to be sparse
Kenyon cells can be related to dopaminergic neurones when an odour is associated with a reward.
What does GAL4 do?
These are transcription factors made by yeast which can be implanted into drosophila genome
This is two roles:
It’s important in studying neurones in the brain. It expresses genes which have a GFP attached. It helps with labelling essentially.
When it transcription factor itself binds to GFP this is referred to as a upstream activating system. (Upstream as the GFP binds to the transcription factor before a gene is expressed.)
Other role?
It induces RNA polymerase which expresses a desired gene, X, in the body
This desired gene is what as GFP attached.
GAL4 can be used to highlight neurones in the brain and express certain genes.
How to highlight a smaller number of neurones? And how to make this gene?
Use the split - GAL4 system which allows for greater specificity. (As in greater specificity as to the neurones targeted by the tagged neurones)
To make this GAL4 is split in two
The GAL4 normally has a DNA binding domain and a activation domain
This is cut in half. Each half can’t do anything alone
Each half of the split GAL4 is expressed by promoters which are found specifically in certain neurones!
When both GAL4 pieces are present with relevant promoters, this allows the split GAL4 to work
you get certain genes expressed which are tagged
Zipper domains on each GAL4 piece helps them come together.
What structures in drosophila were labelled by Split GAL4? What did they tell us about dopamergic neurones?
Split gal4 helps to label neurones in the drosophila’s brains, especially mushroom body output neurones (which had associated kenyon cells which are responsible for olfaction.)
It also showed that there is 1:1 matching of dopaminergic neurones and output neurones , which like reward and output together (note these output neurones are related to smell).
This means that dopaminergic neurones and output neurones dendrites meet at the same place
What did split GAL4 in flies show?
Output neurones labelled by split GAL4 are associated to fly behaviour which cause olfactory learning
This is in conjunction with dopaminergic neurones which help to associate smells with reward
What channels can be inserted into output neurones by the GAL4 system?
Remember GAL4 allows genes to be expressed which have GFPs attached
We can insert optogenetic activators in drosophila output neurones- these are channels that are opened by light
One example is cis crimson
In an experiment drosophila were put in a chamber. One half of the chamber was dark the other had red light. And visa versa
It was found that when there was light, flies moved towards the light and as they did output neurones became active. This suggests there is some kind of reward behaviour to light by the flies.
Therefore there is a link between output neurones (Sensing light) and dopaminergic neurones. (Moving towards the light) thus there must be the same link with olfaction
What changes during learning?
The connection between output neurones (associated with kenyon cells) and dopaminergic neurones.
Describe the experiment where odours and light are associated due to optogenetic activators being in output neurones membranes?
If you pair odour A with a light flash (associated with pain) and then give odour B which isnt associated with light, then allow the fly to choose where it goes.
It goes away from odour A (bad due to light) and towards odour B
Light activates neurones in places which are associated with punishment.
Dopaminergic neurones and mushroom body output neurones in flies are paired together on opposite valences. What does this mean?
The reward dopaminergic neurones are in the same compartment as the avoid output neurones
The punishment dopaminergic neurone are in the same compartments as the approach output neurones.
What happens when learning has begun between the connection of dopaminergic neurones and output neurones supplied by kenyon cells? And what happens to the connections when we do learn?
So note kenyon celled activate avoidance and approach neurones equally before learning has begun.
If we pair an odour with an electric shock (a punishment) you weaken the connections of the punishment dopaminergic neurones onto an approach output neurone. In this way the fly AVOIDS the odour
If you pair an odour with a reward, then the connection between the reward dopaminergic neurone and avoid output neurone weakens. So the fly APPROACHES the odour.
What is important to note about learning and connections between output and dopaminergic neurones?
In learning connections between output neurones and dopaminergic neurones becomes weaker not stronger
I.e remember reward dopamine neurones are related to avoid output neurones. A weakening in this connection causes a fly to move towards a stimulus.
What is temporal pattern of learning? what happens when a odour comes before a shock? What happens if a shock comes before an odour?
When you associate a shock with an odour
If a odour is detected before a shock then an odour is learnt to be bad.
If the odour is detect after the shock then it is learned a good. It is associated with the end of the shock.
How can we use the GAL4 system when it genetically expresses the calcium indicator GCaMP?
Remember GAL4 is a transcription factor which causes a gene to be expressed which has a GFP attached
You can stimulate kenyon cells with electrodes and record avoidance output neurones.
The GAL4 then expressed the calcium indicator GCaMP, which has a GFP attached
When you stimulate an output neurone you see the calcium influx from that output neurone associated with avoidance
The size of the influx of calcium tells you the synaptic strength between kenyon cells and avoidance output neurones
How to artificially stimulate reward dopaminergic neurones?
Do this by stimulating an ATP receptor called p2x2
Putting ATP onto the brain stimulates these neurones.
What is the experiment to test what happens to synapses when you stimulate kenyon cells (which supply output neurones and dopaminergic neurones) via electrical stimulation?
Stimulate dopaminergic neurones and kenyon cells
When these are stimulated separately then there is no alteration is synapse strength
If the dopaminergic stimulation comes right before the kenyon cell stimulation, then you potentiate the synapse and STRENGTHEN the connection between the kenyon cell and output neurone
If you stimulate the kenyon cell and dopaminergic neurone at the same time - then the potentiaion of the synpase becomes a depression - activity between kenyon cell and output neurone and activity between kenyon cell and dopamine neurone becomes the same
What is important to note about reward and avoidance behaviour?
If a odour happens at the same time as a reward then you reduce your avoidance output
What happens if a reward comes before an odour? As in what happens to your avoidance outputs?
You increase your avoidance outputs. The reward coming before the odour means we associate the reward with the ending of a reward.
We can say we potentiate (reduce) this synaptic connection between punhishment and approach so that we avoid something.
What are the two dopamine receptors in flies? What are dopamine receptors as in are they metabotropic? What pathways do these different dopamine receptors signal along?
The two dopamine receptors are DopR1 and DopR2
These receptors a G protein coupled receptors
The DropR1 receptor signal to Gs pathway which eventually causes the production of cAMP.
This is important for learning when a odour proceeds a reward
DropR1 receptors: signal through the Gq pathway. This leads to calcium being released from the endoplasmic reticulum
What is forwards learning in relation to odours?
Forwards learning is when an odour proceeds a reward
What happens if you get rid of the Drop2 receptor? Whats the benefit of forgetting?
Then forgetting doesnt happen as quickly
Memory doesnt decay as it usually would
Benefit of forgetting?
- it helps synapses to be potentiated instead of depressed.
Drop1 receptor: what is it better for? Forming memory or forgetting? Whats the Gs pathway? And what happens when output neurones and dopamine neurones fire at the same time?
The drop1 receptor is better for memory formation
The gs pathway see’s adenyl cyclase be stimulated then forming cAMP
When the output neurone which detects an ODOUR and the dopamine neurone fire at the same time - odour and dopamine become linked.
What is the Gq pathway?
Remember this is membrane breakdown
Gq activates PLC which makes IP3, which makes hits an IP3 receptor on the endoplasmic recticulum of cells
This causes the release of calcium from the ER
How can calcium release from the endoplasmic reticulum in the Gq pathway (in the kenyon cells) be studied? And what is the relationship of calcium in the ER and dopamine stimulation?
GCAP - a GFP can be localised to kenyon cells to detect calcium
When calcium is released from the ER this can be recorded
When a dopaminergic neurone is activated BEFORE an odour, there is a release and thus reduction of calcium in the ER. (This is backward learning (pairing))
However this doesn’t happen when a dopaminergic neurone is activated AFTER a odour (this is forward learning(pairing)). So in this case no calcium is released from the ER.
What feature are conserved for learning?
The cerebellum, the insect mushroom body, the electrosensory lobe in fish.
What is the technical term for the weakening of synapses between output neurones and dopaminergic neurones?
This is depression
Describe the conserved similarities between the mushroom body and the cerebellum:
- just as you have projection neurones coming onto kenyon cells in in flies, you have projection neurones coming onto the cerebellum
In humans the granule cells sample many mossy fibres
The granule cell (humans) and projection neurones (fly) (both are second order neurones) form parallel axons.
What are parallel fibres in humans? And further conserved nature of cerebellum and kenyon cells
These are intercepted by purkinje cells (output neurone)
These prukinje cells get INPUT from masses of parallel granule cells (equivalent of kenyon cell)
The synapses between granule cells (Second order neurones) and purkinje are depressed by teaching signals from climbing fibres.
Synapses between kenyon cells and output neurones are depressed by dopaminergic neurones.
Similarly granule cells and purkinje cells synaptic connections are depressed
Remember purkinje cells (are like output neurones) get input from granule cells (these are the kenyon cell equivalent)
How do electric fish detect prey? And how do they show error correction via the electrosensory lobes?
They emit electric fields and bounce them around the environment, they then listen to echos
The signals from these fish is big and the fishes own electrosensors detect generated pulses
Thus the fish has to ignore its own signals
To do this the fishes granule cells send out the signal and make an efferent copy which tells the fish a signal had been sent out.
The efferent copy depresses the synapse from these active granules Cells onto the purkinje like cells (which carry sensory information out. )
What is error correction? But this concept isnt a LO
This is just the overall mechanisms of weakening / depressing synapses. Such seen in fish with it not detecting its own signal.
