L13 - Modern Questions in Learning and Memory Flashcards

1
Q

How do we make choices?

A

CNS takes sensory input processes it and turns it into motor output
Occurs via a feedback loop

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2
Q

How do we learn?

A

Sensory input combined with evaluator input changes motor output via changes in synaptic connections
Memories allows animals to predict the future

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3
Q

How does classical conditioning work?

A

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
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4
Q

What is the typical apparatus for classical condition training of drosophila?

A
  1. Vacuum sucks air through tube into chamber so flies can smell the odour
  2. Chamber lined with copper grid so electric shocks can be given
    a. Odour A given with shock
    b. Odour B given without shock
  3. Flies should then choose odour B when given the choice to move between the two
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5
Q

How can Drosophila olfactory behaviour be automatically tracked?

A

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

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6
Q

What is the series of neurons after the odour?

A

Odour –> Olfactory receptor neurons –> Projection neurons –> Kenyon cells

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7
Q

Third-order neurons sample second-order neurons to?

A

Respond very selectively to odours

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8
Q

What are the characteristics of Kenyon cells?

A

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

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9
Q

What happens if a fly experiences an odour at the same time as a reward or punishment?

A

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

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10
Q

What is the role of the GAL4/UAS system?

A

Allows artificially expression of arbitrary transgenes in specific cells

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11
Q

GAL4/UAS system method

A
  1. GAL4 is an endogenous transcription factor in yeast
  2. Insert next to an enhancer in genome
  3. Enhancer drives expression of GAL4 in certain cells of the body
    o Wherever enhancer is normally active
  4. GAL4 binds to upstream activating sequence (UAS)
  5. Induces transcription of whatever gene happens to follow UAS
  6. Cross enhancer/Gal4 and UAS/geneX
  7. Progeny has both Gal4 and UAS
  8. Gal4 expressed in certain cells bind to UAS
  9. Recruits RNA polymerase and activates genex transcription
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12
Q

What is the role of the split GAL4 system?

A

Allows greater specificity in which cells express transgene

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13
Q

Split GAL4 system method

A
  1. Split GAL4 into two pieces
    o DNA binding domain – recognises UAS
    o Activation domain – recruits transcription machinery
  2. Either half by itself is not enough to induce transcription
  3. Attach a zipper domain to each domain
  4. Each half expressed under the control of different enhancers
  5. Only where both DNA binding domain and activation are expressed will GAL4 drive expression of the UAS-transgene
  6. Enables you to target a specific neuron in the brain
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14
Q

What is the anatomy of the mushroom body?

A

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

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15
Q

Output neuron characteristics

A

Receive input from Kenyon cells

Dendrites all go to different areas

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16
Q

Dopaminergic neuron characteristics

A

Carry the reward/punishment information

Axons sent to one particular part of the mushroom body

17
Q

How are Kenyon cell axons subdivided?

A

Into compartments by innervation of mushroom body output neurons (MBONs)
Into compartments by innervation of dopaminergic neurons (DANs)

18
Q

Why do MBON and DAN compartments match?

A

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

19
Q

When some MBONs are activated optogenetically is leads to?

A

Approach/avoidance behaviour

20
Q

How are MBONs activated optogenetically?

A

Express a specific optogenetic activator in specific output neurons – red light

  1. Use split GAL4 drivers
  2. Put flies into behaviour chamber where they choose between 4 quadrants
  3. Shine light that activated these neurons in half the chambers
  4. Count amount of time the fly spends on the lit-up part of the chamber
21
Q

Some DANs when activated optogenetically can?

A

Entrain aversive or appetitive memory

22
Q

How are DANs activated optogenetically?

A
  1. Put flies into behaviour chamber where they choose between 4 quadrants
  2. Pump different odours into different quadrants
  3. Then flash red light in dopaminergic neurones during odour A presentation
23
Q

How can you artificially create a memory by optogenetically activating DANs?

A

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

24
Q

DANs are paired with MBONs of?

A

The opposite valence
E.g. a reward dopaminergic neuron is paired with a output neuron that drives avoidance behaviour
- They innervate the same compartment

25
Q

What happens to synapses during learning?

A

Predicts that learning should happen by weakening synapses
When dopaminergic neuron is modifying the synapse between output neuron and Kenyon cells it shouldn’t strengthen the synapse
Strengthening the synapse would be strengthen the wrong behaviour

26
Q

What happens if you pair odour with optogenetic DAN activation?

A

Depress MBON response to trained odour

27
Q

Pairing odour with optogenetic DAN activation method

A
  1. Labelled output neuron with GFP
  2. Record voltage of neuron when fly smells different odours – patch clamp
  3. Express the red light in a singular dopaminergic neuron
    o This activated neuron goes to the same compartment innervated by output neuron with GFP
  4. Paired one odour with artificial activation of dopaminergic neuron
  5. Record voltage again after the training with paired activation of DAN
    o Increase in spiking rate of MCH odour
    o Decrease in spiking rate of OCT odour
28
Q

What are the two possible explanations of why OCT spiking decreases after training?

A

Kenyon cells responding to OCT are suppressed by learning

Synaptic output from OCT-responsive Kenyon cells is suppressed by learning

29
Q

Why is Kenyon cells responding to OCT are suppressed by learning the wrong explanation?

A

Experiments proved this was not the case
Measure the response of Kenyon cell cell bodies – before and after training
Actually their synaptic output that is affected

30
Q

Why is the synaptic output from OCT-responsive Kenyon cells suppressed by learning ?

A

Current clamp - hold the current steady and record the voltage
Voltage clamp – hold the voltage steady and record the current
- Allows you to measure input current from post-synaptic receptors
- Before – strong input current
- After training – weaker input current

31
Q

What could the reason be for the reduction in odour-evoked synaptic currents in MBON after training?

A

Could be due to spike timing-dependent plasticity
Test by blocking spikes in MBON during training using voltage clamp
- Should block post-synaptic neuron spiking – it does
No - spikes in MBON are not required for plasticity

32
Q

DAN-induced depression is specific to?

A

That compartment

The signal from the dopaminergic neuron stays specific to the region of Kenyon cell

33
Q

Plasticity learning rule is different across?

A

Compartments
Multiple reward, punishment, approach, avoidance compartments
Need the ability to form lots of different types of memory

34
Q

What are the different techniques used in modern learning and memory?

A

Quantitative behavioural experiments
GAL4/UAS system – label specific neurons
Optogenetics – artificially activate neurons
Whole-cell patch clamp – record the electrical activity of neurons
Imaging neural activity using genetically encoded calcium indicators

35
Q

What are the 3 conserved structures for learning?

A

Mushroom body
Cerebellum
Electrosensory lobe of weakly electric fish
Have a common basis of fixing errors

36
Q

How does the mushroom body fix errors?

A

Training

37
Q

How does the cerebellum fix errors?

A

Mediates motor learning which is partly about correcting wrong movements
Mossy fibres provide input to granule cells (numerous)
Parallel fibres are intersected by climbing fibres
Climbing fibres modify synapse between granule cells and purkinje cells

38
Q

How does the electrosensory lobe of weakly electric fish fix errors?

A

Signals encoded by eletroreceptors are transformed into a sparse code in granule cells
Electric organ sends an efferent copy, if at same time fish is sensing electric field, it depresses the signal

39
Q

Electrosensory lobe of weakly electric fish structure?

A

Cerebellar like structure

Circuit allows the fish to ignore the electric signals generated by its own electric organ - wrong signals