Learning in Aplysia

Question 1

Learning definition

Answer 1

relatively permanent change in behaviour as a result of experience

Question 2

Memory definition

Answer 2

when current behaviour is under control of past experience

Question 3

Non-associative learning

Answer 3

animals learn about properties of stimulus they encounter

Question 4

Associative learning

Answer 4

Classical (pavlovian) learn about relationship of one stimulus to another. Instrumental learn about the relationship between a stimulus and an action

Question 5

Early proposal for memory?

Answer 5

Reverberating circuits. But results like those of Squire, Slater and Chase 75 showed that ECT did not disrupt memory in the long term

Question 6

Hebb

Answer 6

Postulate for learning. Summarised as cells that fire together wire together

Question 7

Habituation (Non associative)

Answer 7

decrease in response to increasingly repeated non-noxious stimuli

Question 8

Dishabituation (non-associative)

Answer 8

increase in response to a stimulus following its intense presentation

Question 9

Sensitisation (non-associative)

Answer 9

enhanced response to a range of stimuli following an intense or noxious stimulus

Question 10

Sherrington

Answer 10

studied habituation of flexion in animals. Suggested habituation was result of a decrease in function of synapses to motor neurons

Question 11

Spencer and Thompson

Answer 11

Habituation in spinal reflexes of cat. Showed changes at synapse were responsible

Question 12

Kandel

Answer 12

Extensive work on the aplysia earning him the nobel prize

Question 13

Aplysia Californica

Answer 13

20,000 neurons but 200 consistent and major ones. Consistent wiring in all Aplysia

Question 14

Withdrawal reflex

Answer 14

US touch mantle or siphon, UR gill withdrawal

Question 15

Mechanism of habituation

Answer 15

Repeated tactile stimulation and UR decreases. Castellucci et al 1970 (fewer action potentials from gill withdrawal motor neurons with each touch). Castelluci and Kandel 1974 (However sensitivity to artificial neurotransmitter does not decrease and the sensory neurons are still firing a signal). Therefore sensory neurons must be releasing less transmitter

Question 16

Why do sensory neurons release less transmitter?

Answer 16

Klein, Shapiro and Kandel 1980 - less calcium enters presynaptic terminal reducing exocytosis. Gingrich & Byrne, 1985 - depletion of neurotransmitter in sensory neuron

Question 17

Mechanisms of sensitisation

Answer 17

Facilitatory interneurons driven by tail sensory neurons synapse on the axon terminals of siphon sensory neurons. Release of neurotransmitters at axon terminals of siphon sensory neurons modifies their response to siphon stimulation. Presynaptic facilitation

Question 18

Role of interneurons and serotonin

Answer 18

Serotonin mimics sensitisation. Interneurons increase cAMP –> increases depolarisation of presynaptic neuron, allows more calcium into the terminal which increases exocytosis and alters the way calcium participates in mobilizing transmitter vesicles

Question 19

Plasticity

Answer 19

Habituation and sensitisation are the result of a plastic change in the function of neurons but changes can also be long term. Evidence for structural changes of neurons at the synapses for long term effects

Question 20

Pavlovian conditioning

Answer 20

allows animals to learn the relationship between one stimulus and another. Allows us to deal with unobservable mental phenomena (ideas) by studying them through observable behavioural processes

Question 21

Associative learning in Aplysia

Answer 21

CS - light siphon touch, US - tail shock, UR - gill withdrawal and CR strong gill withdrawal

Question 22

Rescorla 1968

Answer 22

Rats presented with a tone and unconditioned stimulus. Only when the CS and US were contingently presented did they produce a CR. Therefore the CS-US paired are associative learners and CS-US unpaired are sensitisation group

Question 23

Differential conditioning

Answer 23

these experiments on the Aplysia prove that it is not sensitisation but conditioning. CS1 and CS2 paired seperately with one US. When tested with CS2 on a CS1 group the response (CR) is lower than the CS2 test would be

Question 24

In paired CS-US training the effect of the US on active CS-UR sensory synapses is much stronger (conditioning). Why?

Answer 24

timing crucial to processes promoting enhancement. in addition to effects of cAMP (see sensitization), a G-protein, adenylate cyclase is increased. one form of this protein binds to calcium (which is in greater abundance) and promotes more production of cAMP. similar processes detected in Drosophila and Hermissenda - mammalian systems seem to differ

Question 25

Mechanism of classical conditioning

Answer 25

US - tail shock excites interneuron. CS - Mantle sensory neuron and interneuron simultaneously active – large change in subsequent sensory neuron transmitter release

Question 26

Memory in Aplysia

Answer 26

Mostly presynaptic effects. No evidence of memory cells or reverberating circuits

Question 27

Bliss and Lomo 1970

Answer 27

long term potentiation. studied slices of hippocampus in vitro. Stimulated axons in the perforant path and measured activity in the dentate gyrus.

Question 28

Properties of LTP

Answer 28

Long term and only occurs when firing of presynaptic neuron is followed by firing of postsynaptic neuron. In Bliss and Lomo experiments a tetanic stimulation bought about a higher EPSP even after a week or month

Question 29

NMDA receptor

Answer 29

LTP most widely studied at these sites. Acts as a coincidence detector only firing when pre and post neurons are. Mg ion displaced when post synaptic neuron is patially depolarised. Allows glutamate to bind and so channel opens allowing calcium ions through. These ions initiate changes in the cell.

Question 30

Evidence for post synaptic changes in LTP

Answer 30

Muller, Joly and Lynch (1988) - showed that the change in synaptic efficacy was mediated by changes in AMPA receptors. AFTER induction of LTP potentiation effect was abolished by blocking AMPA but not NMDA receptors Tocco et al. (1992) measured the number of AMPA and NMDA receptors using radio-labelled ligands and found that LTP changed AMPA, but not NMDA, receptor numbers Blocking protein synthesis prevents LTP (Nguyen, Abel & Kandel, 1994)

Question 31

What will more AMPA receptors do?

Answer 31

More dendritic spines are being produced More AMPA receptors are sitting on these spines, more space for them as well Signal is therefore more likely to be detected

Question 32

Presynaptic changes in LTP

Answer 32

Calcium entering post synaptic cell activates secondary messengers (kinases) and NO is released. Acts as retrograde transporter effecting pre-synaptic cells. Possible by acting on soluble guanyl cyclase-->cyclic GMP-->more glutamate release

Question 33

Glanzman, 1995

Answer 33

Classical conditioning of Aplysia’s withdrawal reflex mediated by Activity-dependent presynaptic facilitation (ADPF): at synapses between central sensory and motor neurons. Postsynaptic mechanism: Hebbian potentiation of the sensorimotor synapses Plasticity at sites other than central monosynaptic sensorimotor connections, including peripheral sites

Question 34

Walters and Byrne

Answer 34

differential conditioning results from different presynaptic effects

Question 35

Carew, Pinsker & Kandel, 1972

Answer 35

Habituation lasts 2 or 3 hours following a single 10-stimulus habitation session, but several such sessions can produce habituation that lasts for weeks

Question 36

Emptage & Carew, 1991

Answer 36

As a result of presynaptic facilitation – sensory fibres from the Aplysia tail synapse on facilitatory serotonergic inter-neurons, which in turn synaps on the buttons of siphon sensory neurons

Question 37

Byrne & Kandel, 1996

Answer 37

Applications of serotonin to Aplysia sensorimotor synapses produces sensitisation lasting minutes to days

Question 38

Cleary, Lee & Byrne, 1998

Answer 38

Long term sensitisation: multiple mechanisms, including lasting increases in motor neuron excitability

Question 39

Carew, Walters & Kandel, 1981

Answer 39

Increase in intensity of the reflex is much greater that if the two stimuli are presented in an unpaired fashion. proves associative nature of effect CC in aplysia

Question 40

Carew, Hawkins & Kandel, 1983

Answer 40

Performed the discriminated classical conditioning tasks

Question 41

Bailey & Chen (1983, 1988)

Answer 41

electron microscopy: long-term habituation & sensitisation leads to structural changes in synaptic terminals of siphon sensory neurons. Sensory neurons:  Fewer active zones of NT release  Smaller active zones of NT release  More synaptic vesicles

Question 42

Pinel

Answer 42

Changes in postsynaptic neurons can be rapid through ion-channel linked receptors or slow and enduring though NT binding G-protein linked receptors and 2d messengers produced as a result

Question 43

Secondary messengers (Pinel)

Answer 43

second messenger increased in buttons of siphon-sensory neurons in response to the serotonin released by tail-shock-activated inter-neurons. o Activates protein kinase A which closes many potassium channels in buttons which increases duration of each action potential which increases influx of calcium & release of NT in response to each touch of siphon.  Byrne & Kandel (1996): this mechanism largely accounts for short-term synaptic facilitation; long-term depends on a second cascade of changes mediated by protein kinase C.

Question 44

Kelso, Ganong & Brown, 1986

Answer 44

LTP Develops only if the firing of the presynaptic neuron is followed by firing of postsynaptic neuron

Question 45

Evidence for LTP in learning and memory (Pinel)

Answer 45

1. LTP can be elicited by low levels of stimulation (mimic normal neural activity) 2. Effects are most prominent in structures that have been implicated in l&m (e.g. hippocampus). 3. Behavioural changes can produce LTP-like changes in Hippocampus (Iriki et al., 1989) 4. Drugs that influence l&m have parallel effects on LTP (Brown et al., 1988; Skelton et al., 1987) 5. Induction of maximal LTP blocks learning of a Morris water maze until LTP has subsided (Castro et al., 1989) 6. Mutant mice that displat little hippocampal LTP have difficulty learning the Morris water maze (Silva et al., 1992)

Question 46

Calcium in LTP

Answer 46

- Calcium probably exerts its effects by activating protein kinases in the neural cytoplasm (Grant & Silva, 1994; Linden & Routtenberg, 1989).