Modern Questions in Learning and Memory

Question 1

How does classical conditioning work? (3)

Answer 1

• Unconditioned stimulus causes an unconditioned response
• Present a conditioned stimulus before the unconditioned stimulus to associate the two
• The conditioned stimulus on its own then causes the response to the unconditioned stimulus = the conditioned response

Question 2

How is classical conditioning done in flies? (3)

Answer 2

• Present odour A and B to the flies
• Associate odour A with an electric shock
• Give the flies a choice between the two odours, the flies avoid odour A and choose odour B

Question 3

Which cells are in the Mushroom body?

Answer 3

Kenyon cells

Question 4

How do drosophila respond sparsely to odours? (3)

Answer 4

• Each Kenyon cell requires multiple simultaneous inputs from projection neurons to reach threshold
• This converts a dense combinatorial code in the projection neurons into a sparse selective code in the Kenyon cells
• Each Kenyon cell responds to a specific combination of odours = selectivity

Question 5

How is reward/punishment associated with odour in drosophila? (2)

Answer 5

• Dopaminergic neurons respond to reward/punishment and modify the output of the Kenyon cells
• This leads to a behaviour associated with the odour

Question 6

How does the GAL4/UAS system work? (3)

Answer 6

• GAL4 is a transcription factor from yeast
• Insert GAL4 into the genome under the control of a promoter which drives expression of GAL4 in specific cells
• GAL4 binds to UAS and causes transcription of whatever is downstream of UAS e.g. GFP etc.

Question 7

What is the UAS?

Answer 7

Upstream activating sequence

Question 8

What is the split-GAL4 system? (3)

Answer 8

• Split the GAL4 gene into the DNA binding domain and the activation domain, put each one under a different promotor
• Very specific subsection of cells in which both promoters will be active so both halves of the GAL4 protein are made, zip together and cause expression of the UAS-transgene
• Allows for greater specificity

Question 9

Which part of the brain in drosophila is responsible for olfactory memory?

Answer 9

Mushroom body

Question 10

What is the structure of the mushroom body? (3)

Answer 10

• Kenyon cells have their dendrites in the calyx
• Kenyon cells send axons down the peduncle
• The axons split to form the vertical lobe and horizontal lobe

Question 11

What are MBONs? (3)

Answer 11

• Mushroom body output neurons
• Receive input from the Kenyon cells
• Encode value (good/bad experience) and lead to approach/avoidance behaviour

Question 12

What are DANs?

Answer 12

Dopaminergic neurons

Question 13

How does olfactory learning occur in the mushroom body? (3)

Answer 13

• Reward DAN axons innervate the same section of the mushroom body as the avoidance MBON dendrites
• Punishment DAN axons innervate the same section of the mushroom body as the approach MBON dendrites
• Learning occurs by the DANs weakening the synapse between the Kenyon cell and the avoid or approach MBON

Question 14

How does the order of reward/punishment and odour change the behavioural response of the flies? (4)

Answer 14

• Flies learn to approach an odour if it is presented after a punishment
• Flies learn to avoid an odour if it is presented before a punishment
• Flies learn to approach an odour if it is presented before a reward
• Flies learn to avoid an odour if it is presented after a reward

Question 15

What mechanism allows for plasticity in olfactory learning in drosophila?

Answer 15

DAN activity coinciding with Kenyon cell activity onto an MBON

Question 16

What are the 2 types of dopamine receptor on Kenyon cells in drosophila?

Answer 16

DopR1 and DopR2

Question 17

What kind of receptors are DopR1 and DopR2?

Answer 17

G protein coupled receptors

Question 18

Which G protein is DopR1 coupled to:

Answer 18

Gs

Question 19

Which G protein is DopR2 coupled to:

Answer 19

Gq

Question 20

What happens when DopR1 is activated? (2)

Answer 20

• Adenylyl cyclase is activated which produces cAMP
• Leads to acquisition of memory

Question 21

What happens when DopR2 is activated? (3)

Answer 21

• PLC is activated which makes IP3 and DAG
• IP3 causes release of Ca2+ from the endoplasmic reticulum
• Leads to forgetting

Question 22

What is the equivalent of adenylyl cyclase in drosophila?

Answer 22

Rutabaga

Question 23

How do the different dopamine receptors respond to different orders of odour and reward? (3)

Answer 23

• When reward happens before odour, DopR1 and DopR2 pathways are both active but DopR2 outweighs DopR1, causing synaptic potentiation i.e. backward learning
• When reward happens after odour, DopR2 is inactive so the DopR1 pathway causes synaptic depression i.e. forward learning
• Learning occurs by DANs weakening the synapse

Question 24

What is EPAC?

Answer 24

Sensor for cAMP

Question 25

What is forward learning?

Answer 25

When conditioning the flies with odour then reward causes them to approach the odour

Question 26

What is backward learning?

Answer 26

When conditioning the flies with reward then odour causes them to avoid the odour

Question 27

How does the DopR2 pathway determine the order of odour and reward and respond specifically? (4)

Answer 27

- IP3 receptor is sensitive to IP3 and Ca2+ - Ca2+ presence signals that the Kenyon cell is active (odour), IP3 presence signals that the DAN is active (reward) - If Ca2+ is present before IP3, channel is locked = no ER Ca2+ released - If IP3 is present before Ca2+, channel is open = ER Ca2+ released

Question 28

How is optogenetics used to study olfactory learning? (3)

Answer 28

- Implant channelrhodopsin in specific neurons - Apply light and see what behaviour results (i.e. approach/avoid etc.) - Can be used to activate specific dopaminergic neurons and 'implant' memories

Question 29

How are quantitative behavioural experiment used to study olfactory learning? (2)

Answer 29

- Conditioning flies to associate an odour with an electric shock - Present a choice of odours to the flies and count how many choose each one

Question 30

What is the equivalent of Kenyon cells in the human cerebellum?

Answer 30

Granule cells

Question 31

What is the equivalent of projection neurons in the human cerebellum?

Answer 31

Mossy fibres

Question 32

How is the mushroom body structure conserved in humans? (3)

Answer 32

- Granule cells converge onto Purkinje cells - The output of granule cells is modified by climbing fibres - Climbing fibres encode an error signal to correct 'wrong' movements

Question 33

How is the cerebellum/mushroom body structure conserved in the electric fish?

Answer 33

Electric organ sends a copy of its own signal that it produced to the Purkinje-like cells so if a signal is received from the granule cells at the same time as the efferent-copy the signal is identified as 'self' and ignored