Modern questions in learning and memory Flashcards

1
Q

What does memory allow us to do?

How is this experimentally shown?

A

Predict the future, but not perfectly

Shown with the conditioning experiment - CS predicts the US

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2
Q

How can flies be conditioned with odours?

A

Provide certain odours with electric shock OR paper soaked in sugar

Learn a specific odour is associated with a positive or negative stimulul

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3
Q

What 2 ways can odours be processed?

A

1) Innate processing - ‘built in’

2) Learned processing - over life experience/memories

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4
Q

What is the processing in the brain of the flies when they smell an odour?

What are the 2nd order and 3rd order neurons?

A
  • Odour activates OLFACTORY RECEPTOR neurons
  • ORN activate PROJECTION NEURONS
  • PN activate KENYON CELLS

2nd order - projection neurons
3rd order - Kenyon cells

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5
Q

How many PN does a Kenyon cell receive input from?

A

MULTIPLE

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6
Q

What causes a Kenyon cell to fire an action potential?

What does this mean?

A

Requires MULTIPLE INPUTS at the SAME TIME from DIFFERENT projection neurons

Means that the Kenyon cells fire very RARELY and SELECTIVELY

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7
Q

What happens (in relation to Kenyon cells) when drosophila experiences an odour at the same time as a reward or punishment?

A

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

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8
Q

What does the simultaneous activation of the Kenyon cells and dopaminergic neurons that carry the reward/punishment information lead to?

A

Change at the OUTPUT synapse of the Kenyon cell (onto the neurons that leads to motor output)

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9
Q

What happens when an CS and a US acts at the same time?

A

SYNERGISTIC activation of a specific biochemical pathway that leads to STRENGTHENING of the synapse

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10
Q

What system allows us to artificially express aribitary transgenes in specific cells?

A

GAL4/UAS system

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11
Q

What is GAL4?

A

A transcription factor from yeast

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12
Q

Describe the method of the GAL4/UAS system

A

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

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13
Q

What is the specific DNA sequence that GAL4 binds to?

A

UAS sequence (upstream activating sequence) - controls the expression of gene X

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14
Q

Why is the GAL4/UAS system hard to do?

A

Relies on finding the perfect enhancer that drives GAL4 in the neurons you want to look at - this is rare

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15
Q

What system shows a greater specificity to the cells want to look at compared to the GAL4/UAS system?

A

The SPLIT-GAL4 system

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16
Q

What do the Kenyon cells in the fly brain make up?

A

The MUSHROOM BODY

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17
Q

How many mushroom bodies are in the fly brain?

A

2 - one either side of the head

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18
Q

How are Kenyon cells organised in the mushroom body?

A

Subdivided into compartments by the innervation of mushroom body output neurons (MBONs)

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19
Q

What are MBONs?

A

Neurons the receive output from the Kenyon cells and sen projections to OTHER parts of the brain

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20
Q

What ‘tiles’ the mushroom body?

A

MBONs and DANs

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21
Q

What do DANs do?

A

Carry the punishment/reward information to a SPECIFIC part of the mushroom body

22
Q

How was the tiling of the mushroom body seen?

A

SPLIT-GAL4 lines

23
Q

Where are the DANs and MBONs present in the mushroom body in relation to each other?

A

1 to 1 matching

ONE DAN enters one compartment and ONE MBON leave the same compartment

24
Q

What happens when activate a specific MBON?

How can this be shown experimentally?

A

Leads to biast approach/avoidance behaviour

  • Shine light onto drosophila that activates a specific neuron
  • See if the drosophila avoids or approaches this light
25
Q

What is optogenetics?

A

Use of light to control cells in living tissue (typically neurons) that have been genetically modified to express light-sensitive ion channels

26
Q

What happens if DANs are activated optogenetically?

How?

A

Can write ARTIFICIAL memories - cause drosophila to approach/avoid

Specific dopaminergic neurons are associated with avoidance/approach behaviour

27
Q

How are specific DANs paired with specific MBONs?

A

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
28
Q

What does the pairing of DANs with MBONs predict?

How?

A

That learning should happen by WEAKENING synapses:

  • Dopamine signalling locally depresses KC-MBON synapses for active KCs –> weakening the synapse
29
Q

What happens in the brain if pair a specific odour with a reward?

What does this allow?

A

Weakening of the AVOIDANCE behaviour

Allowing the fly to APPROACH the odour

30
Q

What determines how a fly behaves towards a certain odour?

A

BALANCE between AVOIDANCE and APPROACH behaviour

31
Q

What happens if approach behaviour in the fly is suppressed?

A

Avoidance will dominate

Fly will AVOID

32
Q

What happens if avoidance behaviour in the fly is suppressed?

A

Approach will dominate

Fly will APPROACH

33
Q

What happens when pair odour optogenetic with DAN activation?

A

Depress MBONs to that specific odour

34
Q

What is learning specific to?

A

The trained odour

Different Kenyon cells respond to odour A compared to odour B

35
Q

What happens to the odour-evoked currents in the MBONs after training?

Why?

A

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)

36
Q

Describe how learning is specific to a trained odour

A

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
37
Q

What is STDP?

A

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

38
Q

Is the reduction in the current and spike rate in the MBON due to STDP?

How is this experimentally shown?

A

NO

Experiment:
- Abolish spikes in the postsynaptic neuron during training
-

39
Q

Is the reduction in the current and spike rate in the MBON due to STDP?

How is this experimentally shown?

A

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
40
Q

What is DAN-induced depression specific to?

A

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
41
Q

What happens to the MBONs of the neighbouring compartment when pair the odour with optogenetic activation of the DANs neuron?

Why?

A

NOTHING happens in the neighbouring compartment

Synaptic plasticity is LOCALISED

42
Q

Describe the plasticity learning in the different compartments of the MB

How is this experimentally shown?

A

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
43
Q

Why is there not just 2 compartments of the mushroom body (one for approach and one for avoid)?

A

In order to have more FLEXIBLE COMPARTMENTS

To be able to create lots of memories (eg. slow to learn/forget easy to learn/forget)

44
Q

What is the GL4/UAS system used for?

A

To label specific neurons

45
Q

What is optogenetics used for?

A
  • To target and artificially activate specific neurons of the brain
  • Leads to behaviour
46
Q

What is the whole-cell patch clamp technique used for?

A

To record the electrical activity in key neurons in behaviour

47
Q

What does the anatomy of a neuron match?

A

Its FUNCTION

48
Q

Is there a conserved structure for error correction?

What is this?

A

Yes

  • Insect mushroom body
  • Cerebellum
  • Electrosensory lobe of weakly electric fish
49
Q

What is the role of the synaptic depression between the KCs and the MBONs?

A

To stop the ‘wrong’ behaviour

eg. reward prevents approach behaviour

50
Q

How is the architecture of the cerebellum similar to that of the mushroom body?

A
  • 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
51
Q

What does the cerebellum mediate?

A

MOTR LEARNING - corrects ‘wrong’ movements