Modern questions in learning and memory Flashcards
What does memory allow us to do?
How is this experimentally shown?
Predict the future, but not perfectly
Shown with the conditioning experiment - CS predicts the US
How can flies be conditioned with odours?
Provide certain odours with electric shock OR paper soaked in sugar
Learn a specific odour is associated with a positive or negative stimulul
What 2 ways can odours be processed?
1) Innate processing - ‘built in’
2) Learned processing - over life experience/memories
What is the processing in the brain of the flies when they smell an odour?
What are the 2nd order and 3rd order neurons?
- Odour activates OLFACTORY RECEPTOR neurons
- ORN activate PROJECTION NEURONS
- PN activate KENYON CELLS
2nd order - projection neurons
3rd order - Kenyon cells
How many PN does a Kenyon cell receive input from?
MULTIPLE
What causes a Kenyon cell to fire an action potential?
What does this mean?
Requires MULTIPLE INPUTS at the SAME TIME from DIFFERENT projection neurons
Means that the Kenyon cells fire very RARELY and SELECTIVELY
What happens (in relation to Kenyon cells) when drosophila experiences an odour at the same time as a reward or punishment?
1) SIMULTANEOUS activation of the kenyon cells that respond SPECIFICALLY to that odour
AND
2) Activation of SOME dopaminergic neurons that carry the reward/punishment information
What does the simultaneous activation of the Kenyon cells and dopaminergic neurons that carry the reward/punishment information lead to?
Change at the OUTPUT synapse of the Kenyon cell (onto the neurons that leads to motor output)
What happens when an CS and a US acts at the same time?
SYNERGISTIC activation of a specific biochemical pathway that leads to STRENGTHENING of the synapse
What system allows us to artificially express aribitary transgenes in specific cells?
GAL4/UAS system
What is GAL4?
A transcription factor from yeast
Describe the method of the GAL4/UAS system
1) Put GAL4 next to an enhancer - drives expression of GAL4
2) Cross together a fly with GAL4 and fly with UAS - progeny have BOTH GAL4 and UAS
3) Progeny - GAL4 expressed and drives the expression of the gene controlled by UAS by recruiting RNA pol
What is the specific DNA sequence that GAL4 binds to?
UAS sequence (upstream activating sequence) - controls the expression of gene X
Why is the GAL4/UAS system hard to do?
Relies on finding the perfect enhancer that drives GAL4 in the neurons you want to look at - this is rare
What system shows a greater specificity to the cells want to look at compared to the GAL4/UAS system?
The SPLIT-GAL4 system
What do the Kenyon cells in the fly brain make up?
The MUSHROOM BODY
How many mushroom bodies are in the fly brain?
2 - one either side of the head
How are Kenyon cells organised in the mushroom body?
Subdivided into compartments by the innervation of mushroom body output neurons (MBONs)
What are MBONs?
Neurons the receive output from the Kenyon cells and sen projections to OTHER parts of the brain
What ‘tiles’ the mushroom body?
MBONs and DANs
What do DANs do?
Carry the punishment/reward information to a SPECIFIC part of the mushroom body
How was the tiling of the mushroom body seen?
SPLIT-GAL4 lines
Where are the DANs and MBONs present in the mushroom body in relation to each other?
1 to 1 matching
ONE DAN enters one compartment and ONE MBON leave the same compartment
What happens when activate a specific MBON?
How can this be shown experimentally?
Leads to biast approach/avoidance behaviour
- Shine light onto drosophila that activates a specific neuron
- See if the drosophila avoids or approaches this light
What is optogenetics?
Use of light to control cells in living tissue (typically neurons) that have been genetically modified to express light-sensitive ion channels
What happens if DANs are activated optogenetically?
How?
Can write ARTIFICIAL memories - cause drosophila to approach/avoid
Specific dopaminergic neurons are associated with avoidance/approach behaviour
How are specific DANs paired with specific MBONs?
DANs are paired (innervate the same compartment) with MBONs of the OPPOSITE valance
- REWARD neuron is paired with output neuron that drives AVOIDANCE behaviour
- PUNISHMENT neuron is paired with output neuron that drives APPROACH behaviour
What does the pairing of DANs with MBONs predict?
How?
That learning should happen by WEAKENING synapses:
- Dopamine signalling locally depresses KC-MBON synapses for active KCs –> weakening the synapse
What happens in the brain if pair a specific odour with a reward?
What does this allow?
Weakening of the AVOIDANCE behaviour
Allowing the fly to APPROACH the odour
What determines how a fly behaves towards a certain odour?
BALANCE between AVOIDANCE and APPROACH behaviour
What happens if approach behaviour in the fly is suppressed?
Avoidance will dominate
Fly will AVOID
What happens if avoidance behaviour in the fly is suppressed?
Approach will dominate
Fly will APPROACH
What happens when pair odour optogenetic with DAN activation?
Depress MBONs to that specific odour
What is learning specific to?
The trained odour
Different Kenyon cells respond to odour A compared to odour B
What happens to the odour-evoked currents in the MBONs after training?
Why?
They are REDUCED (synaptic LTD)
Due to the SYNAPTIC OUTPUT from odour A responsive-KCs being SUPRESSED by learning
(NOT the supression of the KCs themselves)
Describe how learning is specific to a trained odour
Response to a certain odour is only modified if those KCs are active when there is a reward/punishment information along the DANs
- Odour A paired with DA signalling –> only modify the synapses between the KCs to that neuron and the MBON
- Synapse between the KCs (that are responsive to odour B) and the MBON are NOT affected
What is STDP?
Spike timing-dependant plasticity:
- Plasticity that depends upon the TIMING of the spikes in the pre- and post- synaptic neuron
Pre before post –> STRENGTHEN the synapse
Post before pre –> WEAKEN the synapse
Is the reduction in the current and spike rate in the MBON due to STDP?
How is this experimentally shown?
NO
Experiment:
- Abolish spikes in the postsynaptic neuron during training
-
Is the reduction in the current and spike rate in the MBON due to STDP?
How is this experimentally shown?
NO
Experiment:
- Abolish spikes in the postsynaptic neuron during training by voltage clamp
- See if the response of the neuron to the trained odour decreases
What is DAN-induced depression specific to?
The compartment that the DAN innervates:
- DAN innervating one compartment will only modify the synapses between the Kenyon cells and the output neurons of THAT compartment
What happens to the MBONs of the neighbouring compartment when pair the odour with optogenetic activation of the DANs neuron?
Why?
NOTHING happens in the neighbouring compartment
Synaptic plasticity is LOCALISED
Describe the plasticity learning in the different compartments of the MB
How is this experimentally shown?
Different compartments - different plasticity learning
- Specific light training of an output neuron affected that neuron but had to be changed in order to affect an output neuron in a different compartment
Why is there not just 2 compartments of the mushroom body (one for approach and one for avoid)?
In order to have more FLEXIBLE COMPARTMENTS
To be able to create lots of memories (eg. slow to learn/forget easy to learn/forget)
What is the GL4/UAS system used for?
To label specific neurons
What is optogenetics used for?
- To target and artificially activate specific neurons of the brain
- Leads to behaviour
What is the whole-cell patch clamp technique used for?
To record the electrical activity in key neurons in behaviour
What does the anatomy of a neuron match?
Its FUNCTION
Is there a conserved structure for error correction?
What is this?
Yes
- Insect mushroom body
- Cerebellum
- Electrosensory lobe of weakly electric fish
What is the role of the synaptic depression between the KCs and the MBONs?
To stop the ‘wrong’ behaviour
eg. reward prevents approach behaviour
How is the architecture of the cerebellum similar to that of the mushroom body?
- Mossy fibres input to the GRANULE cells (which are like Kenyon cells)
- Granule cells are small and numerous –> form parallel fibres that are intersected by CLIMBING FIBRES (which carry the teaching signal - like the DANs)
- Climbing fibres modify (depress) the synapses between the granule cells and the PURKINJE cells
What does the cerebellum mediate?
MOTR LEARNING - corrects ‘wrong’ movements
