L13 - Modern Questions in Learning and Memory Flashcards
How do we make choices?
CNS takes sensory input processes it and turns it into motor output
Occurs via a feedback loop
How do we learn?
Sensory input combined with evaluator input changes motor output via changes in synaptic connections
Memories allows animals to predict the future
How does classical conditioning work?
The conditioned stimulus should coincide with or precede the unconditioned stimulus
- Learning that the conditioned stimulus predicts the unconditioned stimulus
- If unconditioned stimulus comes before the conditioned stimulus you would not be able to predict or learn the association
What is the typical apparatus for classical condition training of drosophila?
- Vacuum sucks air through tube into chamber so flies can smell the odour
- Chamber lined with copper grid so electric shocks can be given
a. Odour A given with shock
b. Odour B given without shock - Flies should then choose odour B when given the choice to move between the two
How can Drosophila olfactory behaviour be automatically tracked?
Individual flies placed in their own chambers and different odours pumped into either end
Cameras detect the movement of the fly shadows
E.g. Fly avoids orange odour after a while as it is associated with a shock
What is the series of neurons after the odour?
Odour –> Olfactory receptor neurons –> Projection neurons –> Kenyon cells
Third-order neurons sample second-order neurons to?
Respond very selectively to odours
What are the characteristics of Kenyon cells?
Receive input from multiple projection neurons
Require multiple simultaneous inputs to fire - fire very selectively
Sample small regions in PN coding space
Turns a dense combinatorial code into a sparse selective code
Very selective with which odours they respond to
What happens if a fly experiences an odour at the same time as a reward or punishment?
Get simultaneous activation of Kenyon cells that respond to that odour and dopaminergic neurons that carry the reward/punishment info
This leads to change at the output synapse of the Kenyon cell
Convergence of US and CS pathways
What is the role of the GAL4/UAS system?
Allows artificially expression of arbitrary transgenes in specific cells
GAL4/UAS system method
- GAL4 is an endogenous transcription factor in yeast
- Insert next to an enhancer in genome
- Enhancer drives expression of GAL4 in certain cells of the body
o Wherever enhancer is normally active - GAL4 binds to upstream activating sequence (UAS)
- Induces transcription of whatever gene happens to follow UAS
- Cross enhancer/Gal4 and UAS/geneX
- Progeny has both Gal4 and UAS
- Gal4 expressed in certain cells bind to UAS
- Recruits RNA polymerase and activates genex transcription
What is the role of the split GAL4 system?
Allows greater specificity in which cells express transgene
Split GAL4 system method
- Split GAL4 into two pieces
o DNA binding domain – recognises UAS
o Activation domain – recruits transcription machinery - Either half by itself is not enough to induce transcription
- Attach a zipper domain to each domain
- Each half expressed under the control of different enhancers
- Only where both DNA binding domain and activation are expressed will GAL4 drive expression of the UAS-transgene
- Enables you to target a specific neuron in the brain
What is the anatomy of the mushroom body?
Made up of Kenyon cells
You have a mushroom body on each side of the brain
Split GAL4 allowed discovery that the mushroom body structure
is covered by output neurones and dopaminergic neurons
Output neuron characteristics
Receive input from Kenyon cells
Dendrites all go to different areas
Dopaminergic neuron characteristics
Carry the reward/punishment information
Axons sent to one particular part of the mushroom body
How are Kenyon cell axons subdivided?
Into compartments by innervation of mushroom body output neurons (MBONs)
Into compartments by innervation of dopaminergic neurons (DANs)
Why do MBON and DAN compartments match?
These are the compartments defined by the innervation patterns
Roughly 1 to 1 matching of dopaminergic and output neurons to and from the same compartment
When some MBONs are activated optogenetically is leads to?
Approach/avoidance behaviour
How are MBONs activated optogenetically?
Express a specific optogenetic activator in specific output neurons – red light
- Use split GAL4 drivers
- Put flies into behaviour chamber where they choose between 4 quadrants
- Shine light that activated these neurons in half the chambers
- Count amount of time the fly spends on the lit-up part of the chamber
Some DANs when activated optogenetically can?
Entrain aversive or appetitive memory
How are DANs activated optogenetically?
- Put flies into behaviour chamber where they choose between 4 quadrants
- Pump different odours into different quadrants
- Then flash red light in dopaminergic neurones during odour A presentation
How can you artificially create a memory by optogenetically activating DANs?
If a punishment neuron was activated by the red light
Flies start moving towards odour B
Odour A associated with punishment
Only because punishment neuron activated – no punishment was actually given
DANs are paired with MBONs of?
The opposite valence
E.g. a reward dopaminergic neuron is paired with a output neuron that drives avoidance behaviour
- They innervate the same compartment
